David R. Williamson, MSCPharm, PhD

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

Until recently, it was unknown which ICU survivors were at risk of new sedative prescriptions after hospital discharge and if all sedative drug classes were similarly continued. In a recent issue of the journal CHEST®, we addressed the clinical question “Among sedative-naive older adult ICU survivors, how common is the receipt of new and persistent sedative prescriptions, and what factors are associated with the receipt of such prescriptions?” (Burry LD, et al. Chest. 2023;163[6]:1425). We conducted a population-based cohort study using health administrative data between 2003 and 2019 in Ontario, Canada. Among sedative-naive older adults who had survived a hospitalization with ICU admission, we determined the frequency and risk factors associated with filled outpatient sedative prescriptions within 1 week of hospital discharge and persistent sedative prescriptions up to 6 months post-discharge.

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

Until recently, it was unknown which ICU survivors were at risk of new sedative prescriptions after hospital discharge and if all sedative drug classes were similarly continued. In a recent issue of the journal CHEST®, we addressed the clinical question “Among sedative-naive older adult ICU survivors, how common is the receipt of new and persistent sedative prescriptions, and what factors are associated with the receipt of such prescriptions?” (Burry LD, et al. Chest. 2023;163[6]:1425). We conducted a population-based cohort study using health administrative data between 2003 and 2019 in Ontario, Canada. Among sedative-naive older adults who had survived a hospitalization with ICU admission, we determined the frequency and risk factors associated with filled outpatient sedative prescriptions within 1 week of hospital discharge and persistent sedative prescriptions up to 6 months post-discharge.

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.

Patients admitted to ICUs require modifications to their medication regimen due to their critical illness and rapidly changing clinical status. Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.

While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)

Until recently, it was unknown which ICU survivors were at risk of new sedative prescriptions after hospital discharge and if all sedative drug classes were similarly continued. In a recent issue of the journal CHEST®, we addressed the clinical question “Among sedative-naive older adult ICU survivors, how common is the receipt of new and persistent sedative prescriptions, and what factors are associated with the receipt of such prescriptions?” (Burry LD, et al. Chest. 2023;163[6]:1425). We conducted a population-based cohort study using health administrative data between 2003 and 2019 in Ontario, Canada. Among sedative-naive older adults who had survived a hospitalization with ICU admission, we determined the frequency and risk factors associated with filled outpatient sedative prescriptions within 1 week of hospital discharge and persistent sedative prescriptions up to 6 months post-discharge.

The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).

The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.

Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.

In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
 

Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.