A long‐term tunneled subclavian venous catheter of a 32‐year‐old leukaemia patient blocked. Chest x‐ray (CXR) showed a fracture, with the proximal end underneath the first rib and clavicle (Figure 1, arrow, right panel), and distal fragment at the left hila (broken arrow). A CXR 3 months ago showed catheter kinking and narrowing at the same site, constituting the pinch‐off sign (arrow, left panel).1 The broken fragment was retrieved from the left pulmonary artery by cardiac catheterization. Fractured ends were smooth (central insert).

Figure 1

Spontaneous central venous catheter fracture occurs in 0.1% to 1% of cases.2 The catheter fracture is postulated to be related to compression between the clavicle and first rib due to vigorous movement or heavy object lifting,3 activities that should be avoided. Fractures at other sites are exceptional. The pinch‐off sign may precede fracture; if detected, catheter removal is warranted,4 a fact both clinicians and radiologists should be aware of.

A long‐term tunneled subclavian venous catheter of a 32‐year‐old leukaemia patient blocked. Chest x‐ray (CXR) showed a fracture, with the proximal end underneath the first rib and clavicle (Figure 1, arrow, right panel), and distal fragment at the left hila (broken arrow). A CXR 3 months ago showed catheter kinking and narrowing at the same site, constituting the pinch‐off sign (arrow, left panel).1 The broken fragment was retrieved from the left pulmonary artery by cardiac catheterization. Fractured ends were smooth (central insert).

Figure 1

Spontaneous central venous catheter fracture occurs in 0.1% to 1% of cases.2 The catheter fracture is postulated to be related to compression between the clavicle and first rib due to vigorous movement or heavy object lifting,3 activities that should be avoided. Fractures at other sites are exceptional. The pinch‐off sign may precede fracture; if detected, catheter removal is warranted,4 a fact both clinicians and radiologists should be aware of.

A long‐term tunneled subclavian venous catheter of a 32‐year‐old leukaemia patient blocked. Chest x‐ray (CXR) showed a fracture, with the proximal end underneath the first rib and clavicle (Figure 1, arrow, right panel), and distal fragment at the left hila (broken arrow). A CXR 3 months ago showed catheter kinking and narrowing at the same site, constituting the pinch‐off sign (arrow, left panel).1 The broken fragment was retrieved from the left pulmonary artery by cardiac catheterization. Fractured ends were smooth (central insert).

Figure 1

Spontaneous central venous catheter fracture occurs in 0.1% to 1% of cases.2 The catheter fracture is postulated to be related to compression between the clavicle and first rib due to vigorous movement or heavy object lifting,3 activities that should be avoided. Fractures at other sites are exceptional. The pinch‐off sign may precede fracture; if detected, catheter removal is warranted,4 a fact both clinicians and radiologists should be aware of.

If you wish to receive credit for this activity, which begins on the next page, please refer to the website: www. blackwellpublishing.com/cme.

Accreditation and Designation Statement

Blackwell Futura Media Services designates this educational activity for a 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Educational Objectives

Continuous participation in the Journal of Hospital Medicine CME program will enable learners to be better able to:

• Interpret clinical guidelines and their applications for higher quality and more efficient care for all hospitalized patients.

• Describe the standard of care for common illnesses and conditions treated in the hospital; such as pneumonia, COPD exacerbation, acute coronary syndrome, HF exacerbation, glycemic control, venous thromboembolic disease, stroke, etc.

• Discuss evidence‐based recommendations involving transitions of care, including the hospital discharge process.

• Gain insights into the roles of hospitalists as medical educators, researchers, medical ethicists, palliative care providers, and hospital‐based geriatricians.

• Incorporate best practices for hospitalist administration, including quality improvement, patient safety, practice management, leadership, and demonstrating hospitalist value.

• Identify evidence‐based best practices and trends for both adult and pediatric hospital medicine.

Instructions on Receiving Credit

For information on applicability and acceptance of continuing medical education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity during the valid credit period that is noted on the title page.

Follow these steps to earn credit:

• Log on to www.blackwellpublishing.com/cme.

• Read the target audience, learning objectives, and author disclosures.

• Read the article in print or online format.

• Reflect on the article.

• Access the CME Exam, and choose the best answer to each question.

• Complete the required evaluation component of the activity.

If you wish to receive credit for this activity, which begins on the next page, please refer to the website: www. blackwellpublishing.com/cme.

Accreditation and Designation Statement

Blackwell Futura Media Services designates this educational activity for a 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Educational Objectives

Continuous participation in the Journal of Hospital Medicine CME program will enable learners to be better able to:

• Interpret clinical guidelines and their applications for higher quality and more efficient care for all hospitalized patients.

• Describe the standard of care for common illnesses and conditions treated in the hospital; such as pneumonia, COPD exacerbation, acute coronary syndrome, HF exacerbation, glycemic control, venous thromboembolic disease, stroke, etc.

• Discuss evidence‐based recommendations involving transitions of care, including the hospital discharge process.

• Gain insights into the roles of hospitalists as medical educators, researchers, medical ethicists, palliative care providers, and hospital‐based geriatricians.

• Incorporate best practices for hospitalist administration, including quality improvement, patient safety, practice management, leadership, and demonstrating hospitalist value.

• Identify evidence‐based best practices and trends for both adult and pediatric hospital medicine.

Instructions on Receiving Credit

For information on applicability and acceptance of continuing medical education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity during the valid credit period that is noted on the title page.

Follow these steps to earn credit:

• Log on to www.blackwellpublishing.com/cme.

• Read the target audience, learning objectives, and author disclosures.

• Read the article in print or online format.

• Reflect on the article.

• Access the CME Exam, and choose the best answer to each question.

• Complete the required evaluation component of the activity.

If you wish to receive credit for this activity, which begins on the next page, please refer to the website: www. blackwellpublishing.com/cme.

Accreditation and Designation Statement

Blackwell Futura Media Services designates this educational activity for a 1 AMA PRA Category 1 Credit. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Educational Objectives

Continuous participation in the Journal of Hospital Medicine CME program will enable learners to be better able to:

• Interpret clinical guidelines and their applications for higher quality and more efficient care for all hospitalized patients.

• Describe the standard of care for common illnesses and conditions treated in the hospital; such as pneumonia, COPD exacerbation, acute coronary syndrome, HF exacerbation, glycemic control, venous thromboembolic disease, stroke, etc.

• Discuss evidence‐based recommendations involving transitions of care, including the hospital discharge process.

• Gain insights into the roles of hospitalists as medical educators, researchers, medical ethicists, palliative care providers, and hospital‐based geriatricians.

• Incorporate best practices for hospitalist administration, including quality improvement, patient safety, practice management, leadership, and demonstrating hospitalist value.

• Identify evidence‐based best practices and trends for both adult and pediatric hospital medicine.

Instructions on Receiving Credit

For information on applicability and acceptance of continuing medical education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity during the valid credit period that is noted on the title page.

Follow these steps to earn credit:

• Log on to www.blackwellpublishing.com/cme.

• Read the target audience, learning objectives, and author disclosures.

• Read the article in print or online format.

• Reflect on the article.

• Access the CME Exam, and choose the best answer to each question.

• Complete the required evaluation component of the activity.

An 80‐year‐old man with end‐stage renal disease requiring maintenance hemodialysis was admitted to the emergency department (ED) with complaints of fever, generalized fatigue, and lethargy. Presenting electrocardiogram (ECG) revealed normal sinus rhythm at 82 beats per minute (bpm), prolonged PR interval, complete left bundle branch block (LBBB) with wide QRS interval and tall T waves (Figure 1). A baseline ECG done 3 months ago also showed LBBB (Figure 2). In view of the underlying LBBB, changes in the presenting ECG were ignored.

Figure 1

Figure 2

Hemodialysis was planned for the patient. A few hours later, repeat ECG revealed a sine wave pattern suggestive of severe hyperkalemia (Figure 3). Laboratory results were available then and his serum potassium was found to be 6.8 mmol/L. He was started on insulin, dextrose, and calcium gluconate, but he developed cardiorespiratory arrest and died.

Figure 3

Retrospectively, looking at the presenting ECG (Figure 1), it was found that the PR interval was longer, the QRS was broader, and the T waves were taller and more peaked than the baseline ECG (Figure 2).

Discussion

Hyperkalemia is a true medical emergency with potential lethal consequences that must be treated accordingly.1, 2 It can be difficult to diagnose due to the paucity of distinctive signs and symptoms. Any ECG change due to hyperkalemia becomes an indication for stabilizing the myocardium with calcium infusion.

Often, the sequence of repolarization due to myocardial infarction is altered on ECG in patients with baseline LBBB, making it difficult to diagnose accurately. Although it is thought that changes due to electrolyte imbalances will also be masked by the presence of LBBB, there is no evidence supporting this in the literature. Hence, it is wrongly believed that LBBB masks changes due to hyperkalemia. It is important that in patients with suspected electrolyte imbalance, baseline ECG showing LBBB is compared to the presenting ECG. In our patient, the presenting ECG (Figure 1) might not look too impressive, but in comparison to the baseline ECG (Figure 2), the PR interval is longer, QRS is wider, and T waves are more peaked and taller. If the admitting physician had closely compared the presenting ECG (Figure 1) to the baseline ECG (Figure 2), the suspicion of hyperkalemia would have been high.

An 80‐year‐old man with end‐stage renal disease requiring maintenance hemodialysis was admitted to the emergency department (ED) with complaints of fever, generalized fatigue, and lethargy. Presenting electrocardiogram (ECG) revealed normal sinus rhythm at 82 beats per minute (bpm), prolonged PR interval, complete left bundle branch block (LBBB) with wide QRS interval and tall T waves (Figure 1). A baseline ECG done 3 months ago also showed LBBB (Figure 2). In view of the underlying LBBB, changes in the presenting ECG were ignored.

Figure 1

Figure 2

Hemodialysis was planned for the patient. A few hours later, repeat ECG revealed a sine wave pattern suggestive of severe hyperkalemia (Figure 3). Laboratory results were available then and his serum potassium was found to be 6.8 mmol/L. He was started on insulin, dextrose, and calcium gluconate, but he developed cardiorespiratory arrest and died.

Figure 3

Retrospectively, looking at the presenting ECG (Figure 1), it was found that the PR interval was longer, the QRS was broader, and the T waves were taller and more peaked than the baseline ECG (Figure 2).

Discussion

Hyperkalemia is a true medical emergency with potential lethal consequences that must be treated accordingly.1, 2 It can be difficult to diagnose due to the paucity of distinctive signs and symptoms. Any ECG change due to hyperkalemia becomes an indication for stabilizing the myocardium with calcium infusion.

Often, the sequence of repolarization due to myocardial infarction is altered on ECG in patients with baseline LBBB, making it difficult to diagnose accurately. Although it is thought that changes due to electrolyte imbalances will also be masked by the presence of LBBB, there is no evidence supporting this in the literature. Hence, it is wrongly believed that LBBB masks changes due to hyperkalemia. It is important that in patients with suspected electrolyte imbalance, baseline ECG showing LBBB is compared to the presenting ECG. In our patient, the presenting ECG (Figure 1) might not look too impressive, but in comparison to the baseline ECG (Figure 2), the PR interval is longer, QRS is wider, and T waves are more peaked and taller. If the admitting physician had closely compared the presenting ECG (Figure 1) to the baseline ECG (Figure 2), the suspicion of hyperkalemia would have been high.

An 80‐year‐old man with end‐stage renal disease requiring maintenance hemodialysis was admitted to the emergency department (ED) with complaints of fever, generalized fatigue, and lethargy. Presenting electrocardiogram (ECG) revealed normal sinus rhythm at 82 beats per minute (bpm), prolonged PR interval, complete left bundle branch block (LBBB) with wide QRS interval and tall T waves (Figure 1). A baseline ECG done 3 months ago also showed LBBB (Figure 2). In view of the underlying LBBB, changes in the presenting ECG were ignored.

Figure 1

Figure 2

Hemodialysis was planned for the patient. A few hours later, repeat ECG revealed a sine wave pattern suggestive of severe hyperkalemia (Figure 3). Laboratory results were available then and his serum potassium was found to be 6.8 mmol/L. He was started on insulin, dextrose, and calcium gluconate, but he developed cardiorespiratory arrest and died.

Figure 3

Retrospectively, looking at the presenting ECG (Figure 1), it was found that the PR interval was longer, the QRS was broader, and the T waves were taller and more peaked than the baseline ECG (Figure 2).

Discussion

Hyperkalemia is a true medical emergency with potential lethal consequences that must be treated accordingly.1, 2 It can be difficult to diagnose due to the paucity of distinctive signs and symptoms. Any ECG change due to hyperkalemia becomes an indication for stabilizing the myocardium with calcium infusion.

Often, the sequence of repolarization due to myocardial infarction is altered on ECG in patients with baseline LBBB, making it difficult to diagnose accurately. Although it is thought that changes due to electrolyte imbalances will also be masked by the presence of LBBB, there is no evidence supporting this in the literature. Hence, it is wrongly believed that LBBB masks changes due to hyperkalemia. It is important that in patients with suspected electrolyte imbalance, baseline ECG showing LBBB is compared to the presenting ECG. In our patient, the presenting ECG (Figure 1) might not look too impressive, but in comparison to the baseline ECG (Figure 2), the PR interval is longer, QRS is wider, and T waves are more peaked and taller. If the admitting physician had closely compared the presenting ECG (Figure 1) to the baseline ECG (Figure 2), the suspicion of hyperkalemia would have been high.

The successful integration of hospitalists in academic health science centers (AHSCs) has been identified as one of the most challenging areas for the hospitalist movement.1, 2 This has been based on a concern that many hospitalists lack academic and research skills, lack mentorship, and may have little time to develop academic careers because of the significant time they spend in clinical care.

A recent survey highlighted that the pediatric hospitalist workforce is in its infancy and additional perspectives, such as from hospitalists themselves, are essential for a more complete picture of the current state of pediatric hospital medicine.3 Hospitalists have had a long history in Canada.4 The Hospital for Sick Children, Toronto, Canada, has had a Division of Pediatric Medicine since 1981, with hospitalists, as we now know them, from inception. This provided a rich resource to explore pediatric hospital medicine in the academic context and from hospitalists themselves. The objective of this survey was to explore the characteristics, practice, and perceptions of pediatric hospital medicine in an AHSC. Locally, we hoped the results would inform the division on program development, training, and faculty career development. Externally, the findings could contribute to a body of knowledge on the evolving role of pediatric hospitalists and provide insight into opportunities for better integration into AHSCs.

Methods

Results

Eighteen of 20 (90%) faculty responded to the questionnaire. The results are presented by the domains of the questionnaire, as follows.

Discussion

Freed et al.3 recently conducted a survey of U.S. pediatric hospitalist program directors from a diverse range of settings (ie, teaching vs. nonteaching, free‐standing vs. hospital system, children's hospitals vs. non‐children's hospitals).3 These investigators found that the majority of programs had employed hospitalists for less than 5 years (compared with our program, 30 years); employed 1 to 5 hospitalists (compared with our program, 20); and 25% of programs indicated their hospitalists averaged greater than 5 years on the job (compared with our program, average 10 years on the job). Maniscalco et al.6 conducted a survey in 2007 of hospitalists in a similarly diverse range of settings, found that the mean number of years on the job was 6 and found similar clinical and teaching roles. They also found that the need for advanced training in administration, research, education, and quality improvement was high. Further, we were able to examine academic roles and perceptions of hospital medicine as a career in an AHSC at an individual level. This survey, however, was limited by sampling from a single institution.

Almost all faculty identified an area of focus in addition to clinical care. Educational activities occurred at all levels: undergraduate, residency, fellowship, and continuing medical education. Faculty were engaged in research activities. Hospitalists provide care on all inpatient units as a consultant specialist in general medical care. For example, we have designed a collaborative model of care with the interventional radiology team to comanage children who require image‐guided interventions, such as gastrostomy, chest tube, and central venous line insertions.7 One further area that deserves mention is the leadership of hospitalists in outpatient care of children, especially hospital intense populations, in collaboration with their primary care provider. These groups of children are often medically and socially complex, require repeated and intense hospital resources (including diagnostic testing, subspecialty consultation, and hospitalization), and require generalist care to manage them from a family centered perspective.

A significant proportion of the faculty in this survey acquired advanced academic training. The formal training of hospitalist physicians is in its infancy. A recent work documenting the domains of training for academic general pediatric fellowship in leadership, education, and research seems to be most appropriate for the nonclinical foundation for pediatric academic hospitalists.8

Few studies have examined academic hospitalists' perceptions on the minimum and maximum time per year suitable for clinical service. This undoubtedly will vary depending on the institution, program and financial structure, patient load and complexity, call requirements, academic commitments, and stage of development. Faculty surveyed in this study felt a range of 11 to 32 weeks of clinical inpatient attending per year was ideal. This is consistent with the expert panel recommendations of the Society of Hospital Medicine. What may be equally important to determine is the maximum number of continuous weeks attending on the PMIU.

There have been 3 full‐time faculty who have left the division (all to community hospitalbased generalist practices with academic affiliations) and 1 who has changed from a full‐time to a part‐time role in the division. Most faculty surveyed intended to continue their career as a hospitalist. They identified several positive and satisfying aspects to the career, including relationships with peers, stable salary, numerous opportunities for scholarly work in a young field, and generalist care. Hoff et al.9 described a national US survey of hospitalists in all adult medicine settings that examined personal characteristics, and work‐related attitudes. Similarly, they found that hospital medicine was a source of positive social and professional work experiences related to interactions with peers, patients and families, and coworkers. In the current study, perceived disadvantages to a hospitalist career were burnout, lack of recognition and respect, and lack of long‐term relationships with patients. Hoff et al.9 noted that 37% were burnt out or at risk of burnout, which is less than in the fields of critical care medicine and emergency medicine.

The identified barriers to establishing a career were related to development of an academic focus, balance between clinical and nonclinical time, and the system for career advancement. Few other studies have examined these career issues for hospitalists in the academic setting. Several authors have discussed career issues for clinician‐educators in the US,10, 11 including metrics for promotion and recognition by institutions. Alternate methods have been proposed for promotion, aside from research and education, such as creative professional activity or clinical excellence.12 The developing field of hospital medicine faces similar challenges as individual hospitalists and the specialty itself works to align with the academic mission.1315

The division and hospitalist program have evolved over more than 2 decades to fulfill strategic goals and respond to changing external factors (Table 3). Contextual factors that have supported this evolution and that may be unique to our academic environment merit mention. First, the departments' physicians work in a within a single‐payer universal healthcare system that in some ways is similar to a single‐payer health maintenance organization. The ultimate governance is provided by the provincial Ministry of Health, which is funded through taxation. Second, through an alternative funding plan (AFP) with the provincial government, block funding is providing in lieu of fee for service clinical care that funds physician salaries for clinical work, research, education, and administrative activities.16 Third, the department has a career development compensation program (CDCP) that has an explicit job activity profile which is aligned with the role of hospitaliststhe clinician‐specialist profilewho have a predominate commitment to provide, advance, and promote excellence in clinical care with contributions to education and/or research.16 The compensation and evaluation process for hospitalists is the same as other members in the department. While further refinement of this system is ongoing, this program has demonstrated a support for all roles (ie, clinical, education, and research).17

Furthermore, several divisional factors have contributed to the viability of hospitalism within our generalist division. First, hospitalists were integrated into, rather than segregated from the division. Second, hospitalists have the opportunity to engage in diverse clinical activities. Wachter and Goldman18 advocate for hospitalist participation in outpatient care to provide variety and to cement their relationship with their generalist division. Third, a fellowship training program was established in 1992 that integrated principles of academic general pediatrics and hospitalism. Fourth, career development in education, research, and, more recently, quality improvement is fostered.

In summary, the faculty of an established pediatric hospitalist program have diverse and unique clinical, leadership, and scholarly contributions to the academic mission of the department. In order to further promote integration, several issues should be addressed, including optimal training, time allocated to nonclinical activities, systems for career development and promotion of hospitalist faculty, and mentorship. Finally, it is important that leaders in pediatric hospital medicine and general pediatrics engage the larger academic community to strengthen the role and contributions of hospitalists in AHSCs.

The successful integration of hospitalists in academic health science centers (AHSCs) has been identified as one of the most challenging areas for the hospitalist movement.1, 2 This has been based on a concern that many hospitalists lack academic and research skills, lack mentorship, and may have little time to develop academic careers because of the significant time they spend in clinical care.

A recent survey highlighted that the pediatric hospitalist workforce is in its infancy and additional perspectives, such as from hospitalists themselves, are essential for a more complete picture of the current state of pediatric hospital medicine.3 Hospitalists have had a long history in Canada.4 The Hospital for Sick Children, Toronto, Canada, has had a Division of Pediatric Medicine since 1981, with hospitalists, as we now know them, from inception. This provided a rich resource to explore pediatric hospital medicine in the academic context and from hospitalists themselves. The objective of this survey was to explore the characteristics, practice, and perceptions of pediatric hospital medicine in an AHSC. Locally, we hoped the results would inform the division on program development, training, and faculty career development. Externally, the findings could contribute to a body of knowledge on the evolving role of pediatric hospitalists and provide insight into opportunities for better integration into AHSCs.

Methods

Results

Eighteen of 20 (90%) faculty responded to the questionnaire. The results are presented by the domains of the questionnaire, as follows.

Discussion

Freed et al.3 recently conducted a survey of U.S. pediatric hospitalist program directors from a diverse range of settings (ie, teaching vs. nonteaching, free‐standing vs. hospital system, children's hospitals vs. non‐children's hospitals).3 These investigators found that the majority of programs had employed hospitalists for less than 5 years (compared with our program, 30 years); employed 1 to 5 hospitalists (compared with our program, 20); and 25% of programs indicated their hospitalists averaged greater than 5 years on the job (compared with our program, average 10 years on the job). Maniscalco et al.6 conducted a survey in 2007 of hospitalists in a similarly diverse range of settings, found that the mean number of years on the job was 6 and found similar clinical and teaching roles. They also found that the need for advanced training in administration, research, education, and quality improvement was high. Further, we were able to examine academic roles and perceptions of hospital medicine as a career in an AHSC at an individual level. This survey, however, was limited by sampling from a single institution.

Almost all faculty identified an area of focus in addition to clinical care. Educational activities occurred at all levels: undergraduate, residency, fellowship, and continuing medical education. Faculty were engaged in research activities. Hospitalists provide care on all inpatient units as a consultant specialist in general medical care. For example, we have designed a collaborative model of care with the interventional radiology team to comanage children who require image‐guided interventions, such as gastrostomy, chest tube, and central venous line insertions.7 One further area that deserves mention is the leadership of hospitalists in outpatient care of children, especially hospital intense populations, in collaboration with their primary care provider. These groups of children are often medically and socially complex, require repeated and intense hospital resources (including diagnostic testing, subspecialty consultation, and hospitalization), and require generalist care to manage them from a family centered perspective.

A significant proportion of the faculty in this survey acquired advanced academic training. The formal training of hospitalist physicians is in its infancy. A recent work documenting the domains of training for academic general pediatric fellowship in leadership, education, and research seems to be most appropriate for the nonclinical foundation for pediatric academic hospitalists.8

Few studies have examined academic hospitalists' perceptions on the minimum and maximum time per year suitable for clinical service. This undoubtedly will vary depending on the institution, program and financial structure, patient load and complexity, call requirements, academic commitments, and stage of development. Faculty surveyed in this study felt a range of 11 to 32 weeks of clinical inpatient attending per year was ideal. This is consistent with the expert panel recommendations of the Society of Hospital Medicine. What may be equally important to determine is the maximum number of continuous weeks attending on the PMIU.

There have been 3 full‐time faculty who have left the division (all to community hospitalbased generalist practices with academic affiliations) and 1 who has changed from a full‐time to a part‐time role in the division. Most faculty surveyed intended to continue their career as a hospitalist. They identified several positive and satisfying aspects to the career, including relationships with peers, stable salary, numerous opportunities for scholarly work in a young field, and generalist care. Hoff et al.9 described a national US survey of hospitalists in all adult medicine settings that examined personal characteristics, and work‐related attitudes. Similarly, they found that hospital medicine was a source of positive social and professional work experiences related to interactions with peers, patients and families, and coworkers. In the current study, perceived disadvantages to a hospitalist career were burnout, lack of recognition and respect, and lack of long‐term relationships with patients. Hoff et al.9 noted that 37% were burnt out or at risk of burnout, which is less than in the fields of critical care medicine and emergency medicine.

The identified barriers to establishing a career were related to development of an academic focus, balance between clinical and nonclinical time, and the system for career advancement. Few other studies have examined these career issues for hospitalists in the academic setting. Several authors have discussed career issues for clinician‐educators in the US,10, 11 including metrics for promotion and recognition by institutions. Alternate methods have been proposed for promotion, aside from research and education, such as creative professional activity or clinical excellence.12 The developing field of hospital medicine faces similar challenges as individual hospitalists and the specialty itself works to align with the academic mission.1315

The division and hospitalist program have evolved over more than 2 decades to fulfill strategic goals and respond to changing external factors (Table 3). Contextual factors that have supported this evolution and that may be unique to our academic environment merit mention. First, the departments' physicians work in a within a single‐payer universal healthcare system that in some ways is similar to a single‐payer health maintenance organization. The ultimate governance is provided by the provincial Ministry of Health, which is funded through taxation. Second, through an alternative funding plan (AFP) with the provincial government, block funding is providing in lieu of fee for service clinical care that funds physician salaries for clinical work, research, education, and administrative activities.16 Third, the department has a career development compensation program (CDCP) that has an explicit job activity profile which is aligned with the role of hospitaliststhe clinician‐specialist profilewho have a predominate commitment to provide, advance, and promote excellence in clinical care with contributions to education and/or research.16 The compensation and evaluation process for hospitalists is the same as other members in the department. While further refinement of this system is ongoing, this program has demonstrated a support for all roles (ie, clinical, education, and research).17

Furthermore, several divisional factors have contributed to the viability of hospitalism within our generalist division. First, hospitalists were integrated into, rather than segregated from the division. Second, hospitalists have the opportunity to engage in diverse clinical activities. Wachter and Goldman18 advocate for hospitalist participation in outpatient care to provide variety and to cement their relationship with their generalist division. Third, a fellowship training program was established in 1992 that integrated principles of academic general pediatrics and hospitalism. Fourth, career development in education, research, and, more recently, quality improvement is fostered.

In summary, the faculty of an established pediatric hospitalist program have diverse and unique clinical, leadership, and scholarly contributions to the academic mission of the department. In order to further promote integration, several issues should be addressed, including optimal training, time allocated to nonclinical activities, systems for career development and promotion of hospitalist faculty, and mentorship. Finally, it is important that leaders in pediatric hospital medicine and general pediatrics engage the larger academic community to strengthen the role and contributions of hospitalists in AHSCs.

The successful integration of hospitalists in academic health science centers (AHSCs) has been identified as one of the most challenging areas for the hospitalist movement.1, 2 This has been based on a concern that many hospitalists lack academic and research skills, lack mentorship, and may have little time to develop academic careers because of the significant time they spend in clinical care.

A recent survey highlighted that the pediatric hospitalist workforce is in its infancy and additional perspectives, such as from hospitalists themselves, are essential for a more complete picture of the current state of pediatric hospital medicine.3 Hospitalists have had a long history in Canada.4 The Hospital for Sick Children, Toronto, Canada, has had a Division of Pediatric Medicine since 1981, with hospitalists, as we now know them, from inception. This provided a rich resource to explore pediatric hospital medicine in the academic context and from hospitalists themselves. The objective of this survey was to explore the characteristics, practice, and perceptions of pediatric hospital medicine in an AHSC. Locally, we hoped the results would inform the division on program development, training, and faculty career development. Externally, the findings could contribute to a body of knowledge on the evolving role of pediatric hospitalists and provide insight into opportunities for better integration into AHSCs.

Methods

Results

Eighteen of 20 (90%) faculty responded to the questionnaire. The results are presented by the domains of the questionnaire, as follows.

Discussion

Freed et al.3 recently conducted a survey of U.S. pediatric hospitalist program directors from a diverse range of settings (ie, teaching vs. nonteaching, free‐standing vs. hospital system, children's hospitals vs. non‐children's hospitals).3 These investigators found that the majority of programs had employed hospitalists for less than 5 years (compared with our program, 30 years); employed 1 to 5 hospitalists (compared with our program, 20); and 25% of programs indicated their hospitalists averaged greater than 5 years on the job (compared with our program, average 10 years on the job). Maniscalco et al.6 conducted a survey in 2007 of hospitalists in a similarly diverse range of settings, found that the mean number of years on the job was 6 and found similar clinical and teaching roles. They also found that the need for advanced training in administration, research, education, and quality improvement was high. Further, we were able to examine academic roles and perceptions of hospital medicine as a career in an AHSC at an individual level. This survey, however, was limited by sampling from a single institution.

Almost all faculty identified an area of focus in addition to clinical care. Educational activities occurred at all levels: undergraduate, residency, fellowship, and continuing medical education. Faculty were engaged in research activities. Hospitalists provide care on all inpatient units as a consultant specialist in general medical care. For example, we have designed a collaborative model of care with the interventional radiology team to comanage children who require image‐guided interventions, such as gastrostomy, chest tube, and central venous line insertions.7 One further area that deserves mention is the leadership of hospitalists in outpatient care of children, especially hospital intense populations, in collaboration with their primary care provider. These groups of children are often medically and socially complex, require repeated and intense hospital resources (including diagnostic testing, subspecialty consultation, and hospitalization), and require generalist care to manage them from a family centered perspective.

A significant proportion of the faculty in this survey acquired advanced academic training. The formal training of hospitalist physicians is in its infancy. A recent work documenting the domains of training for academic general pediatric fellowship in leadership, education, and research seems to be most appropriate for the nonclinical foundation for pediatric academic hospitalists.8

Few studies have examined academic hospitalists' perceptions on the minimum and maximum time per year suitable for clinical service. This undoubtedly will vary depending on the institution, program and financial structure, patient load and complexity, call requirements, academic commitments, and stage of development. Faculty surveyed in this study felt a range of 11 to 32 weeks of clinical inpatient attending per year was ideal. This is consistent with the expert panel recommendations of the Society of Hospital Medicine. What may be equally important to determine is the maximum number of continuous weeks attending on the PMIU.

There have been 3 full‐time faculty who have left the division (all to community hospitalbased generalist practices with academic affiliations) and 1 who has changed from a full‐time to a part‐time role in the division. Most faculty surveyed intended to continue their career as a hospitalist. They identified several positive and satisfying aspects to the career, including relationships with peers, stable salary, numerous opportunities for scholarly work in a young field, and generalist care. Hoff et al.9 described a national US survey of hospitalists in all adult medicine settings that examined personal characteristics, and work‐related attitudes. Similarly, they found that hospital medicine was a source of positive social and professional work experiences related to interactions with peers, patients and families, and coworkers. In the current study, perceived disadvantages to a hospitalist career were burnout, lack of recognition and respect, and lack of long‐term relationships with patients. Hoff et al.9 noted that 37% were burnt out or at risk of burnout, which is less than in the fields of critical care medicine and emergency medicine.

The identified barriers to establishing a career were related to development of an academic focus, balance between clinical and nonclinical time, and the system for career advancement. Few other studies have examined these career issues for hospitalists in the academic setting. Several authors have discussed career issues for clinician‐educators in the US,10, 11 including metrics for promotion and recognition by institutions. Alternate methods have been proposed for promotion, aside from research and education, such as creative professional activity or clinical excellence.12 The developing field of hospital medicine faces similar challenges as individual hospitalists and the specialty itself works to align with the academic mission.1315

The division and hospitalist program have evolved over more than 2 decades to fulfill strategic goals and respond to changing external factors (Table 3). Contextual factors that have supported this evolution and that may be unique to our academic environment merit mention. First, the departments' physicians work in a within a single‐payer universal healthcare system that in some ways is similar to a single‐payer health maintenance organization. The ultimate governance is provided by the provincial Ministry of Health, which is funded through taxation. Second, through an alternative funding plan (AFP) with the provincial government, block funding is providing in lieu of fee for service clinical care that funds physician salaries for clinical work, research, education, and administrative activities.16 Third, the department has a career development compensation program (CDCP) that has an explicit job activity profile which is aligned with the role of hospitaliststhe clinician‐specialist profilewho have a predominate commitment to provide, advance, and promote excellence in clinical care with contributions to education and/or research.16 The compensation and evaluation process for hospitalists is the same as other members in the department. While further refinement of this system is ongoing, this program has demonstrated a support for all roles (ie, clinical, education, and research).17

Furthermore, several divisional factors have contributed to the viability of hospitalism within our generalist division. First, hospitalists were integrated into, rather than segregated from the division. Second, hospitalists have the opportunity to engage in diverse clinical activities. Wachter and Goldman18 advocate for hospitalist participation in outpatient care to provide variety and to cement their relationship with their generalist division. Third, a fellowship training program was established in 1992 that integrated principles of academic general pediatrics and hospitalism. Fourth, career development in education, research, and, more recently, quality improvement is fostered.

In summary, the faculty of an established pediatric hospitalist program have diverse and unique clinical, leadership, and scholarly contributions to the academic mission of the department. In order to further promote integration, several issues should be addressed, including optimal training, time allocated to nonclinical activities, systems for career development and promotion of hospitalist faculty, and mentorship. Finally, it is important that leaders in pediatric hospital medicine and general pediatrics engage the larger academic community to strengthen the role and contributions of hospitalists in AHSCs.

Lactic acidosis (LA) is common in hospitalized patients and is associated with a high mortality.1, 2 Commonly, it is defined as a lactic acid concentration greater than 5 mmol/L with a pH less than 7.35.3 There are no evidence‐based guidelines for the treatment of LA despite progress in our understanding of its pathophysiology.36 This is not surprising, given the uncertainty regarding the impact of LA itself on clinical outcomes. In this regard, it is interesting to note that, despite its well‐recognized role as a marker of tissue hypoxia, lactate accumulation appears to have beneficial effects and may function as an adaptive mechanism. This raises the possibility that therapy directed at altering this adaptation may be detrimental. Pursuing correction of the pH in LA has been shown to have untoward physiologic effects. These and other ambiguities in the pathophysiology and treatment of LA are the focus of this review.

Lactate Metabolism

The body produces approximately 1400 mmol of lactate daily.7 Lactate is derived from the metabolism of pyruvate through an anaerobic reaction that occurs in all tissues (Figure 1). The liver is the primary site of lactate clearance and can metabolize up to 100 mmol per hour under normal conditions.8 There, lactate is converted to glucose to serve as an energy source during periods of hypoxia (Figure 2).9

Figure 1

Figure 2

Approximately 20% to 30% of the daily lactate load is metabolized by the kidneys.10, 11 Renal clearance is increased in acidosis12 and is maintained even in the presence of low renal perfusion.10, 12, 13 Renal lactate clearance is primarily through metabolism and not excretion.10, 14

LA Subtypes

Generally, lactic acid accumulation results from excess lactic acid production and not from reduced clearance.15 In cases of fulminant liver failure, it is due to a combination of decreased clearance and tissue hypoxia.16 In the setting of tissue hypoxia, an impairment of mitochondrial oxidative capacity results in the accumulation of pyruvate and generation of lactate. Lactic acid accumulation through this mechanism has historically been described as Type A LA.7 Hence, in critically ill patients lactate has traditionally been viewed as a marker of tissue hypoxia.15, 1721 Hyperlactatemia without tissue hypoxia has been referred to as type B LA. This is seen in a variety of circumstances. In sepsis, for example, several studies have shown lactic acid accumulation, despite adequate oxygen delivery.2224

Hyperlactatemia may also occur in cases of pure mitochondrial dysfunction, which can be induced by commonly prescribed medications such as the biguanides, nucleoside analog reverse‐transcriptase inhibitors (NRTIs), and linezolid.2527 Alternatively, lactate generation from metabolism of agents such as propylene glycol is possible. Finally, excessive lactate generation may occur following stress due to altered carbohydrate metabolism, or with respiratory alkalosis.2831

Lactate: A Metabolic Adaptation

Lactate was traditionally considered only as a marker of tissue hypoxia and anaerobic metabolism.17 This is certainly the case in situations of poor perfusion such as cardiogenic,15, 18 vasopressor‐resistant,19 or hypovolemic shock.20, 21

Alternative explanations for lactic acid accumulation, without tissue hypoperfusion, include catecholamine‐induced alterations in glycolysis,32, 33 mitochondrial disturbances,3436 and increased pyruvate production combined with increased glucose entry into cells.24, 37 In addition, the activity of an enzyme regulating lactate metabolism, pyruvate dehydrogenase kinase, increases in sepsis.38 This enzyme inactivates the pyruvate dehydrogenase (PDH) complex, which metabolizes pyruvate. Pyruvate and lactate may accumulate as a result. These changes partly explain the generation of LA in sepsis, independent of any effect of diminished tissue perfusion.

Recognizing the body's tendency toward homeostasis, it is appealing to speculate that lactate accumulation is adaptive.9 A number of findings support this. For example, lactate may act to shuttle energy between organs, or between cell types in the same organ. The astrocyteneuron lactate shuttle and the spermatogenic lactate shuttle are 2 examples of lactate's valuable effects on cellular metabolism.39 In the astrocyteneuron lactate shuttle, astrocytes support the increased metabolic demands of neurons through lactic acid production.40 Specifically, the neurotransmitter glutamate is released by the neurons and taken up by the astrocytes. Astrocytes produce lactate, which then moves back to the neuron to be used as an energy source. Glutamine, also released by the astrocytes, leads to the regeneration of glutamate and the potential to restart the cycle.39

Animal and human studies have suggested that, in periods of stress, lactate is the preferential energy substrate in the brain.4144 The usefulness of increased lactate production routinely seen in sepsis may thus represent multiple adaptive processes aimed primarily at improving the delivery of energy substrates. Thus, therapeutic strategies aimed specifically at lowering lactic acid levels may prove to have deleterious effects on cellular metabolism.

Impact of LA on Morbidity and Mortality

The poor prognosis in patients with LA is well recognized.2, 4548 For example, in a study of 126 patients with various causes of LA, the median survival was 38.5 hours and 30‐day survival was 17%.2

Studies have revealed that LA with low pH is associated with adverse effects on the cardiovascular system, particularly a decrease in cardiac contractility.49, 50 This effect is particularly prominent with a pH below 7.20. In contrast, acidosis in animal models has been shown to limit myocardial infarct size after reperfusion.51, 52 Variable effects of LA on cell death have been found. A worsening of apoptosis in myocytes has been noted;53 alternatively, protection from hypoxic injury in hepatocytes and myocardium has been observed.52, 54 Thus, although LA is associated with poor outcomes in human studies,2, 4547 it is still unclear to what extent lactic acid accumulation is a marker of severe illness, an independent effector of pathology, or a mechanism with the potential to serve a protective role.

Available data indicate that lactate itself is not harmful. Studies on infusion of lactate solutions to postoperative patients was shown to be safe.55 Also, the fact that lactate generation in states of respiratory alkalosis, stress, or altered carbohydrate metabolism without sepsis is not associated with worse outcomes supports the fact that lactic acid alone may not be maladaptive.2831

Similarly, low pH is not necessarily maladaptive. In the postictal state,56 diabetic ketoacidosis,57 spontaneous respiratory acidosis,58 or permissive hypercapnia,59 low blood pH is not deleterious.

In summary, LA is associated with poor outcomes, and indirect evidence suggests that it is the underlying causative condition rather than the low pH or the lactate that is responsible for the dire outcomes.

Treatment of LA with Sodium Bicarbonate

Since excessive lactic acid generation is accompanied by consumption of plasma bicarbonate and a fall in plasma pH, sodium bicarbonate has been long proposed as a treatment for LA. While theoretically appealing, this strategy has not been validated by studies in animals or humans. Indeed, bicarbonate administration in LA often has been shown to be detrimental.60, 61 The adverse effects of bicarbonate administration in LA, while initially paradoxical, have a number of possible explanations.

First, bicarbonate administration can induce a reduction in intracellular pH.60, 62, 63 The mechanism involves bicarbonate's effect to increase carbon dioxide (CO₂) generation through mass action effect. Because the cell membrane is more permeable to CO₂ than to bicarbonate, intracellular pH falls.64, 65 In sepsis, this intracellular/extracellular pH discrepancy may be more pronounced due to alterations in blood flow.66 Other reports on outcomes of intracellular pH with bicarbonate therapy show variable effects.6772

Second, to the extent that bicarbonate administration raises extracellular pH, it is associated with a reduction in ionized calcium concentration, since the binding of calcium to albumin is pH dependent.73 A sodium bicarbonate load administered to patients with LA was associated with a significant fall in ionized calcium concentration, whereas a sodium chloride load was not.1 This can affect cardiac function, as the latter varies proportionally with calcium levels.74

Third, bicarbonate administration may reduce tissue oxygen delivery since the affinity of hemoglobin for oxygen increases as pH rises (Bohr effect).75 The administration of bicarbonate worsened systemic oxygen consumption in one study76 and decreased oxygen delivery in another.75

Fourth, bicarbonate administration may indirectly increase intracellular calcium concentration. Low intracellular pH (see above) stimulates proton efflux by way of proton transporters and exchangers, increasing intracellular sodium content.77 A high cell sodium content then may increase intracellular calcium, through the Na/Ca exchanger, impairing cellular function.7779 Compounding this, the reduced function of the Na/H ATPase as a regulator of intracellular sodium in sepsis may not be adequate to limit cell swelling.77

Against this background of mechanistic concerns with the use of bicarbonate treatment, it is not surprising that clinical outcomes have been inconsistent at best. In animal models of LA, the use of sodium bicarbonate has either negative effects on cardiac output60, 72 or no significant hemodynamic effect when compared to sodium chloride infusion.67, 80, 81 One animal study did show some benefit with sodium bicarbonate compared to saline, though all animals subsequently died.50

In humans, sodium bicarbonate was studied in 2 randomized trials of sepsis‐induced LA.1, 82 In a study by Cooper et al.,1 14 critically‐ill patients received sequential infusions of sodium bicarbonate or sodium chloride. Neither solution was superior to the other in terms of hemodynamic improvement. No benefit was noted even when analysis was limited to those with very low pH (<7.2). Mathieu et al.82 randomized 10 critically‐ill patients to sequential infusion of either sodium bicarbonate or sodium chloride. Similarly, no significant difference in hemodynamic variables was noted.

When taken together, these studies evaluating sodium bicarbonate in LA fail to show convincing benefit and raise serious questions about its detrimental effects. Extracellular pH may be a misleading marker of success in the treatment of LA, given its direct influence by sodium bicarbonate administration.

Treatment of LA and Use of Other Buffers

Other buffers (Carbicarb, dichloroacetate, and tromethamine [THAM]) have been studied for treatment of LA. Human studies have not shown superiority of any of the buffers as far as improving pH,83, 84 hemodynamics, or survival.85

Treatment of LA by Renal Replacement Therapy

Renal replacement therapy (RRT; dialysis and its variants) has been studied for the treatment of severe acidosis. RRT has a number of theoretical advantages over purely medical therapies in the treatment of LA: it can deliver large quantities of base without contributing to volume overload; it can directly remove lactate from the plasma; and it can mitigate the effect of alkalinization on ionized calcium concentration by delivering calcium.

In critically ill patients with intact liver function, continuous venovenous hemofiltration (CVVH) appears to contribute very little (less then 3%) to overall lactate clearance.86 While outcome studies are limited, continuous dialysis modalities consistently show improved resolution of acidosis of various types when compared to intermittent modalities.87, 88 As described above, this is related to base administration and is not a surprising finding. There are no studies comparing RRT and medical therapy with respect to clinical outcomes in patients with LA.

Special Situations

Conclusions

Many studies note the association between LA and adverse outcomes.2, 4547 Though metabolic acidosis from elevated lactate levels may negatively affect organ function, the evidence supporting therapy specifically aimed at increasing pH in these settings is consistently poor.3, 127 Limitations have included small numbers of subjects,1, 82 variable outcomes studied, and the inability to assess intracellular metabolic stability.1, 61 When taking these factors into account it is hard to justify aggressive treatment of LA with mechanisms aimed at raising pH. Literature on the treatment of patients with LA and very low pH (below 7.2) is even more limited.

Moreover, lactate elevations may not represent tissue hypoperfusion. Lactate may have an important role in improving energy metabolism. This represents 1 additional reason to be hesitant when attempting to normalize pH in LA; we may be disrupting the body's physiologic response to sepsis. A conflict for clinicians emerges, however, as lactate is often used to define tissue ischemia. Obviously, more specific markers of tissue hypoperfusion would be ideal.

Bicarbonate therapy is an understandably attractive means to improve the acidemia, but there are serious mechanistic concerns with it use. Moreover, neither animal nor human studies, limited as they may be, show a convincing benefit. LA in the setting of acute kidney injury may be best treated with renal replacement therapy with bicarbonate‐based buffers, but controlled trials are lacking.

A number of commonly used drugs can cause LA. A heightened awareness on the part of clinicians will lead to prompt recognition of these cases, and timely treatment.

Lactic acidosis (LA) is common in hospitalized patients and is associated with a high mortality.1, 2 Commonly, it is defined as a lactic acid concentration greater than 5 mmol/L with a pH less than 7.35.3 There are no evidence‐based guidelines for the treatment of LA despite progress in our understanding of its pathophysiology.36 This is not surprising, given the uncertainty regarding the impact of LA itself on clinical outcomes. In this regard, it is interesting to note that, despite its well‐recognized role as a marker of tissue hypoxia, lactate accumulation appears to have beneficial effects and may function as an adaptive mechanism. This raises the possibility that therapy directed at altering this adaptation may be detrimental. Pursuing correction of the pH in LA has been shown to have untoward physiologic effects. These and other ambiguities in the pathophysiology and treatment of LA are the focus of this review.

Lactate Metabolism

The body produces approximately 1400 mmol of lactate daily.7 Lactate is derived from the metabolism of pyruvate through an anaerobic reaction that occurs in all tissues (Figure 1). The liver is the primary site of lactate clearance and can metabolize up to 100 mmol per hour under normal conditions.8 There, lactate is converted to glucose to serve as an energy source during periods of hypoxia (Figure 2).9

Figure 1

Figure 2

Approximately 20% to 30% of the daily lactate load is metabolized by the kidneys.10, 11 Renal clearance is increased in acidosis12 and is maintained even in the presence of low renal perfusion.10, 12, 13 Renal lactate clearance is primarily through metabolism and not excretion.10, 14

LA Subtypes

Generally, lactic acid accumulation results from excess lactic acid production and not from reduced clearance.15 In cases of fulminant liver failure, it is due to a combination of decreased clearance and tissue hypoxia.16 In the setting of tissue hypoxia, an impairment of mitochondrial oxidative capacity results in the accumulation of pyruvate and generation of lactate. Lactic acid accumulation through this mechanism has historically been described as Type A LA.7 Hence, in critically ill patients lactate has traditionally been viewed as a marker of tissue hypoxia.15, 1721 Hyperlactatemia without tissue hypoxia has been referred to as type B LA. This is seen in a variety of circumstances. In sepsis, for example, several studies have shown lactic acid accumulation, despite adequate oxygen delivery.2224

Hyperlactatemia may also occur in cases of pure mitochondrial dysfunction, which can be induced by commonly prescribed medications such as the biguanides, nucleoside analog reverse‐transcriptase inhibitors (NRTIs), and linezolid.2527 Alternatively, lactate generation from metabolism of agents such as propylene glycol is possible. Finally, excessive lactate generation may occur following stress due to altered carbohydrate metabolism, or with respiratory alkalosis.2831

Lactate: A Metabolic Adaptation

Lactate was traditionally considered only as a marker of tissue hypoxia and anaerobic metabolism.17 This is certainly the case in situations of poor perfusion such as cardiogenic,15, 18 vasopressor‐resistant,19 or hypovolemic shock.20, 21

Alternative explanations for lactic acid accumulation, without tissue hypoperfusion, include catecholamine‐induced alterations in glycolysis,32, 33 mitochondrial disturbances,3436 and increased pyruvate production combined with increased glucose entry into cells.24, 37 In addition, the activity of an enzyme regulating lactate metabolism, pyruvate dehydrogenase kinase, increases in sepsis.38 This enzyme inactivates the pyruvate dehydrogenase (PDH) complex, which metabolizes pyruvate. Pyruvate and lactate may accumulate as a result. These changes partly explain the generation of LA in sepsis, independent of any effect of diminished tissue perfusion.

Recognizing the body's tendency toward homeostasis, it is appealing to speculate that lactate accumulation is adaptive.9 A number of findings support this. For example, lactate may act to shuttle energy between organs, or between cell types in the same organ. The astrocyteneuron lactate shuttle and the spermatogenic lactate shuttle are 2 examples of lactate's valuable effects on cellular metabolism.39 In the astrocyteneuron lactate shuttle, astrocytes support the increased metabolic demands of neurons through lactic acid production.40 Specifically, the neurotransmitter glutamate is released by the neurons and taken up by the astrocytes. Astrocytes produce lactate, which then moves back to the neuron to be used as an energy source. Glutamine, also released by the astrocytes, leads to the regeneration of glutamate and the potential to restart the cycle.39

Animal and human studies have suggested that, in periods of stress, lactate is the preferential energy substrate in the brain.4144 The usefulness of increased lactate production routinely seen in sepsis may thus represent multiple adaptive processes aimed primarily at improving the delivery of energy substrates. Thus, therapeutic strategies aimed specifically at lowering lactic acid levels may prove to have deleterious effects on cellular metabolism.

Impact of LA on Morbidity and Mortality

The poor prognosis in patients with LA is well recognized.2, 4548 For example, in a study of 126 patients with various causes of LA, the median survival was 38.5 hours and 30‐day survival was 17%.2

Studies have revealed that LA with low pH is associated with adverse effects on the cardiovascular system, particularly a decrease in cardiac contractility.49, 50 This effect is particularly prominent with a pH below 7.20. In contrast, acidosis in animal models has been shown to limit myocardial infarct size after reperfusion.51, 52 Variable effects of LA on cell death have been found. A worsening of apoptosis in myocytes has been noted;53 alternatively, protection from hypoxic injury in hepatocytes and myocardium has been observed.52, 54 Thus, although LA is associated with poor outcomes in human studies,2, 4547 it is still unclear to what extent lactic acid accumulation is a marker of severe illness, an independent effector of pathology, or a mechanism with the potential to serve a protective role.

Available data indicate that lactate itself is not harmful. Studies on infusion of lactate solutions to postoperative patients was shown to be safe.55 Also, the fact that lactate generation in states of respiratory alkalosis, stress, or altered carbohydrate metabolism without sepsis is not associated with worse outcomes supports the fact that lactic acid alone may not be maladaptive.2831

Similarly, low pH is not necessarily maladaptive. In the postictal state,56 diabetic ketoacidosis,57 spontaneous respiratory acidosis,58 or permissive hypercapnia,59 low blood pH is not deleterious.

In summary, LA is associated with poor outcomes, and indirect evidence suggests that it is the underlying causative condition rather than the low pH or the lactate that is responsible for the dire outcomes.

Treatment of LA with Sodium Bicarbonate

Since excessive lactic acid generation is accompanied by consumption of plasma bicarbonate and a fall in plasma pH, sodium bicarbonate has been long proposed as a treatment for LA. While theoretically appealing, this strategy has not been validated by studies in animals or humans. Indeed, bicarbonate administration in LA often has been shown to be detrimental.60, 61 The adverse effects of bicarbonate administration in LA, while initially paradoxical, have a number of possible explanations.

First, bicarbonate administration can induce a reduction in intracellular pH.60, 62, 63 The mechanism involves bicarbonate's effect to increase carbon dioxide (CO₂) generation through mass action effect. Because the cell membrane is more permeable to CO₂ than to bicarbonate, intracellular pH falls.64, 65 In sepsis, this intracellular/extracellular pH discrepancy may be more pronounced due to alterations in blood flow.66 Other reports on outcomes of intracellular pH with bicarbonate therapy show variable effects.6772

Second, to the extent that bicarbonate administration raises extracellular pH, it is associated with a reduction in ionized calcium concentration, since the binding of calcium to albumin is pH dependent.73 A sodium bicarbonate load administered to patients with LA was associated with a significant fall in ionized calcium concentration, whereas a sodium chloride load was not.1 This can affect cardiac function, as the latter varies proportionally with calcium levels.74

Third, bicarbonate administration may reduce tissue oxygen delivery since the affinity of hemoglobin for oxygen increases as pH rises (Bohr effect).75 The administration of bicarbonate worsened systemic oxygen consumption in one study76 and decreased oxygen delivery in another.75

Fourth, bicarbonate administration may indirectly increase intracellular calcium concentration. Low intracellular pH (see above) stimulates proton efflux by way of proton transporters and exchangers, increasing intracellular sodium content.77 A high cell sodium content then may increase intracellular calcium, through the Na/Ca exchanger, impairing cellular function.7779 Compounding this, the reduced function of the Na/H ATPase as a regulator of intracellular sodium in sepsis may not be adequate to limit cell swelling.77

Against this background of mechanistic concerns with the use of bicarbonate treatment, it is not surprising that clinical outcomes have been inconsistent at best. In animal models of LA, the use of sodium bicarbonate has either negative effects on cardiac output60, 72 or no significant hemodynamic effect when compared to sodium chloride infusion.67, 80, 81 One animal study did show some benefit with sodium bicarbonate compared to saline, though all animals subsequently died.50

In humans, sodium bicarbonate was studied in 2 randomized trials of sepsis‐induced LA.1, 82 In a study by Cooper et al.,1 14 critically‐ill patients received sequential infusions of sodium bicarbonate or sodium chloride. Neither solution was superior to the other in terms of hemodynamic improvement. No benefit was noted even when analysis was limited to those with very low pH (<7.2). Mathieu et al.82 randomized 10 critically‐ill patients to sequential infusion of either sodium bicarbonate or sodium chloride. Similarly, no significant difference in hemodynamic variables was noted.

When taken together, these studies evaluating sodium bicarbonate in LA fail to show convincing benefit and raise serious questions about its detrimental effects. Extracellular pH may be a misleading marker of success in the treatment of LA, given its direct influence by sodium bicarbonate administration.

Treatment of LA and Use of Other Buffers

Other buffers (Carbicarb, dichloroacetate, and tromethamine [THAM]) have been studied for treatment of LA. Human studies have not shown superiority of any of the buffers as far as improving pH,83, 84 hemodynamics, or survival.85

Treatment of LA by Renal Replacement Therapy

Renal replacement therapy (RRT; dialysis and its variants) has been studied for the treatment of severe acidosis. RRT has a number of theoretical advantages over purely medical therapies in the treatment of LA: it can deliver large quantities of base without contributing to volume overload; it can directly remove lactate from the plasma; and it can mitigate the effect of alkalinization on ionized calcium concentration by delivering calcium.

In critically ill patients with intact liver function, continuous venovenous hemofiltration (CVVH) appears to contribute very little (less then 3%) to overall lactate clearance.86 While outcome studies are limited, continuous dialysis modalities consistently show improved resolution of acidosis of various types when compared to intermittent modalities.87, 88 As described above, this is related to base administration and is not a surprising finding. There are no studies comparing RRT and medical therapy with respect to clinical outcomes in patients with LA.

Special Situations

Conclusions

Many studies note the association between LA and adverse outcomes.2, 4547 Though metabolic acidosis from elevated lactate levels may negatively affect organ function, the evidence supporting therapy specifically aimed at increasing pH in these settings is consistently poor.3, 127 Limitations have included small numbers of subjects,1, 82 variable outcomes studied, and the inability to assess intracellular metabolic stability.1, 61 When taking these factors into account it is hard to justify aggressive treatment of LA with mechanisms aimed at raising pH. Literature on the treatment of patients with LA and very low pH (below 7.2) is even more limited.

Moreover, lactate elevations may not represent tissue hypoperfusion. Lactate may have an important role in improving energy metabolism. This represents 1 additional reason to be hesitant when attempting to normalize pH in LA; we may be disrupting the body's physiologic response to sepsis. A conflict for clinicians emerges, however, as lactate is often used to define tissue ischemia. Obviously, more specific markers of tissue hypoperfusion would be ideal.

Bicarbonate therapy is an understandably attractive means to improve the acidemia, but there are serious mechanistic concerns with it use. Moreover, neither animal nor human studies, limited as they may be, show a convincing benefit. LA in the setting of acute kidney injury may be best treated with renal replacement therapy with bicarbonate‐based buffers, but controlled trials are lacking.

A number of commonly used drugs can cause LA. A heightened awareness on the part of clinicians will lead to prompt recognition of these cases, and timely treatment.

Lactic acidosis (LA) is common in hospitalized patients and is associated with a high mortality.1, 2 Commonly, it is defined as a lactic acid concentration greater than 5 mmol/L with a pH less than 7.35.3 There are no evidence‐based guidelines for the treatment of LA despite progress in our understanding of its pathophysiology.36 This is not surprising, given the uncertainty regarding the impact of LA itself on clinical outcomes. In this regard, it is interesting to note that, despite its well‐recognized role as a marker of tissue hypoxia, lactate accumulation appears to have beneficial effects and may function as an adaptive mechanism. This raises the possibility that therapy directed at altering this adaptation may be detrimental. Pursuing correction of the pH in LA has been shown to have untoward physiologic effects. These and other ambiguities in the pathophysiology and treatment of LA are the focus of this review.

Lactate Metabolism

The body produces approximately 1400 mmol of lactate daily.7 Lactate is derived from the metabolism of pyruvate through an anaerobic reaction that occurs in all tissues (Figure 1). The liver is the primary site of lactate clearance and can metabolize up to 100 mmol per hour under normal conditions.8 There, lactate is converted to glucose to serve as an energy source during periods of hypoxia (Figure 2).9

Figure 1

Figure 2

Approximately 20% to 30% of the daily lactate load is metabolized by the kidneys.10, 11 Renal clearance is increased in acidosis12 and is maintained even in the presence of low renal perfusion.10, 12, 13 Renal lactate clearance is primarily through metabolism and not excretion.10, 14

LA Subtypes

Generally, lactic acid accumulation results from excess lactic acid production and not from reduced clearance.15 In cases of fulminant liver failure, it is due to a combination of decreased clearance and tissue hypoxia.16 In the setting of tissue hypoxia, an impairment of mitochondrial oxidative capacity results in the accumulation of pyruvate and generation of lactate. Lactic acid accumulation through this mechanism has historically been described as Type A LA.7 Hence, in critically ill patients lactate has traditionally been viewed as a marker of tissue hypoxia.15, 1721 Hyperlactatemia without tissue hypoxia has been referred to as type B LA. This is seen in a variety of circumstances. In sepsis, for example, several studies have shown lactic acid accumulation, despite adequate oxygen delivery.2224

Hyperlactatemia may also occur in cases of pure mitochondrial dysfunction, which can be induced by commonly prescribed medications such as the biguanides, nucleoside analog reverse‐transcriptase inhibitors (NRTIs), and linezolid.2527 Alternatively, lactate generation from metabolism of agents such as propylene glycol is possible. Finally, excessive lactate generation may occur following stress due to altered carbohydrate metabolism, or with respiratory alkalosis.2831

Lactate: A Metabolic Adaptation

Lactate was traditionally considered only as a marker of tissue hypoxia and anaerobic metabolism.17 This is certainly the case in situations of poor perfusion such as cardiogenic,15, 18 vasopressor‐resistant,19 or hypovolemic shock.20, 21

Alternative explanations for lactic acid accumulation, without tissue hypoperfusion, include catecholamine‐induced alterations in glycolysis,32, 33 mitochondrial disturbances,3436 and increased pyruvate production combined with increased glucose entry into cells.24, 37 In addition, the activity of an enzyme regulating lactate metabolism, pyruvate dehydrogenase kinase, increases in sepsis.38 This enzyme inactivates the pyruvate dehydrogenase (PDH) complex, which metabolizes pyruvate. Pyruvate and lactate may accumulate as a result. These changes partly explain the generation of LA in sepsis, independent of any effect of diminished tissue perfusion.

Recognizing the body's tendency toward homeostasis, it is appealing to speculate that lactate accumulation is adaptive.9 A number of findings support this. For example, lactate may act to shuttle energy between organs, or between cell types in the same organ. The astrocyteneuron lactate shuttle and the spermatogenic lactate shuttle are 2 examples of lactate's valuable effects on cellular metabolism.39 In the astrocyteneuron lactate shuttle, astrocytes support the increased metabolic demands of neurons through lactic acid production.40 Specifically, the neurotransmitter glutamate is released by the neurons and taken up by the astrocytes. Astrocytes produce lactate, which then moves back to the neuron to be used as an energy source. Glutamine, also released by the astrocytes, leads to the regeneration of glutamate and the potential to restart the cycle.39

Animal and human studies have suggested that, in periods of stress, lactate is the preferential energy substrate in the brain.4144 The usefulness of increased lactate production routinely seen in sepsis may thus represent multiple adaptive processes aimed primarily at improving the delivery of energy substrates. Thus, therapeutic strategies aimed specifically at lowering lactic acid levels may prove to have deleterious effects on cellular metabolism.

Impact of LA on Morbidity and Mortality

The poor prognosis in patients with LA is well recognized.2, 4548 For example, in a study of 126 patients with various causes of LA, the median survival was 38.5 hours and 30‐day survival was 17%.2

Studies have revealed that LA with low pH is associated with adverse effects on the cardiovascular system, particularly a decrease in cardiac contractility.49, 50 This effect is particularly prominent with a pH below 7.20. In contrast, acidosis in animal models has been shown to limit myocardial infarct size after reperfusion.51, 52 Variable effects of LA on cell death have been found. A worsening of apoptosis in myocytes has been noted;53 alternatively, protection from hypoxic injury in hepatocytes and myocardium has been observed.52, 54 Thus, although LA is associated with poor outcomes in human studies,2, 4547 it is still unclear to what extent lactic acid accumulation is a marker of severe illness, an independent effector of pathology, or a mechanism with the potential to serve a protective role.

Available data indicate that lactate itself is not harmful. Studies on infusion of lactate solutions to postoperative patients was shown to be safe.55 Also, the fact that lactate generation in states of respiratory alkalosis, stress, or altered carbohydrate metabolism without sepsis is not associated with worse outcomes supports the fact that lactic acid alone may not be maladaptive.2831

Similarly, low pH is not necessarily maladaptive. In the postictal state,56 diabetic ketoacidosis,57 spontaneous respiratory acidosis,58 or permissive hypercapnia,59 low blood pH is not deleterious.

In summary, LA is associated with poor outcomes, and indirect evidence suggests that it is the underlying causative condition rather than the low pH or the lactate that is responsible for the dire outcomes.

Treatment of LA with Sodium Bicarbonate

Since excessive lactic acid generation is accompanied by consumption of plasma bicarbonate and a fall in plasma pH, sodium bicarbonate has been long proposed as a treatment for LA. While theoretically appealing, this strategy has not been validated by studies in animals or humans. Indeed, bicarbonate administration in LA often has been shown to be detrimental.60, 61 The adverse effects of bicarbonate administration in LA, while initially paradoxical, have a number of possible explanations.

First, bicarbonate administration can induce a reduction in intracellular pH.60, 62, 63 The mechanism involves bicarbonate's effect to increase carbon dioxide (CO₂) generation through mass action effect. Because the cell membrane is more permeable to CO₂ than to bicarbonate, intracellular pH falls.64, 65 In sepsis, this intracellular/extracellular pH discrepancy may be more pronounced due to alterations in blood flow.66 Other reports on outcomes of intracellular pH with bicarbonate therapy show variable effects.6772

Second, to the extent that bicarbonate administration raises extracellular pH, it is associated with a reduction in ionized calcium concentration, since the binding of calcium to albumin is pH dependent.73 A sodium bicarbonate load administered to patients with LA was associated with a significant fall in ionized calcium concentration, whereas a sodium chloride load was not.1 This can affect cardiac function, as the latter varies proportionally with calcium levels.74

Third, bicarbonate administration may reduce tissue oxygen delivery since the affinity of hemoglobin for oxygen increases as pH rises (Bohr effect).75 The administration of bicarbonate worsened systemic oxygen consumption in one study76 and decreased oxygen delivery in another.75

Fourth, bicarbonate administration may indirectly increase intracellular calcium concentration. Low intracellular pH (see above) stimulates proton efflux by way of proton transporters and exchangers, increasing intracellular sodium content.77 A high cell sodium content then may increase intracellular calcium, through the Na/Ca exchanger, impairing cellular function.7779 Compounding this, the reduced function of the Na/H ATPase as a regulator of intracellular sodium in sepsis may not be adequate to limit cell swelling.77

Against this background of mechanistic concerns with the use of bicarbonate treatment, it is not surprising that clinical outcomes have been inconsistent at best. In animal models of LA, the use of sodium bicarbonate has either negative effects on cardiac output60, 72 or no significant hemodynamic effect when compared to sodium chloride infusion.67, 80, 81 One animal study did show some benefit with sodium bicarbonate compared to saline, though all animals subsequently died.50

In humans, sodium bicarbonate was studied in 2 randomized trials of sepsis‐induced LA.1, 82 In a study by Cooper et al.,1 14 critically‐ill patients received sequential infusions of sodium bicarbonate or sodium chloride. Neither solution was superior to the other in terms of hemodynamic improvement. No benefit was noted even when analysis was limited to those with very low pH (<7.2). Mathieu et al.82 randomized 10 critically‐ill patients to sequential infusion of either sodium bicarbonate or sodium chloride. Similarly, no significant difference in hemodynamic variables was noted.

When taken together, these studies evaluating sodium bicarbonate in LA fail to show convincing benefit and raise serious questions about its detrimental effects. Extracellular pH may be a misleading marker of success in the treatment of LA, given its direct influence by sodium bicarbonate administration.

Treatment of LA and Use of Other Buffers

Other buffers (Carbicarb, dichloroacetate, and tromethamine [THAM]) have been studied for treatment of LA. Human studies have not shown superiority of any of the buffers as far as improving pH,83, 84 hemodynamics, or survival.85

Treatment of LA by Renal Replacement Therapy

Renal replacement therapy (RRT; dialysis and its variants) has been studied for the treatment of severe acidosis. RRT has a number of theoretical advantages over purely medical therapies in the treatment of LA: it can deliver large quantities of base without contributing to volume overload; it can directly remove lactate from the plasma; and it can mitigate the effect of alkalinization on ionized calcium concentration by delivering calcium.

In critically ill patients with intact liver function, continuous venovenous hemofiltration (CVVH) appears to contribute very little (less then 3%) to overall lactate clearance.86 While outcome studies are limited, continuous dialysis modalities consistently show improved resolution of acidosis of various types when compared to intermittent modalities.87, 88 As described above, this is related to base administration and is not a surprising finding. There are no studies comparing RRT and medical therapy with respect to clinical outcomes in patients with LA.

Special Situations

Conclusions

Many studies note the association between LA and adverse outcomes.2, 4547 Though metabolic acidosis from elevated lactate levels may negatively affect organ function, the evidence supporting therapy specifically aimed at increasing pH in these settings is consistently poor.3, 127 Limitations have included small numbers of subjects,1, 82 variable outcomes studied, and the inability to assess intracellular metabolic stability.1, 61 When taking these factors into account it is hard to justify aggressive treatment of LA with mechanisms aimed at raising pH. Literature on the treatment of patients with LA and very low pH (below 7.2) is even more limited.

Moreover, lactate elevations may not represent tissue hypoperfusion. Lactate may have an important role in improving energy metabolism. This represents 1 additional reason to be hesitant when attempting to normalize pH in LA; we may be disrupting the body's physiologic response to sepsis. A conflict for clinicians emerges, however, as lactate is often used to define tissue ischemia. Obviously, more specific markers of tissue hypoperfusion would be ideal.

Bicarbonate therapy is an understandably attractive means to improve the acidemia, but there are serious mechanistic concerns with it use. Moreover, neither animal nor human studies, limited as they may be, show a convincing benefit. LA in the setting of acute kidney injury may be best treated with renal replacement therapy with bicarbonate‐based buffers, but controlled trials are lacking.

A number of commonly used drugs can cause LA. A heightened awareness on the part of clinicians will lead to prompt recognition of these cases, and timely treatment.