Hospitals provide acute inpatient care all day and every day. Nonetheless, a number of studies have shown that weekend care may have lower quality than care delivered on weekdays. [1, 2, 3, 4, 5, 6, 7] Weekend care has been associated with increased mortality among patients suffering from a number of conditions [4, 5, 6, 7, 8, 9, 10] and in a number of clinical settings. [11, 12, 13, 14] Findings of poor outcomes on weekends are not universal, though exceptions occur typically in settings where services and clinical staffing are fairly constant throughout the week, such as intensive care units with on‐site intensivists. [15, 16, 17]

These differences in quality and outcomes suggest that there is a difference in intensity of care over the course of the week. Initiatives to address this important safety issue would be strengthened if a shared metric existed to describe the intensity of care provided at a given time of day or day of the week. However, few measures of global hospital intensity of care exist. The metrics that have been developed are limited by measuring only 1 aspect of care delivery, such as weekend nurse staffing, [18] by requiring extensive chart abstraction, [19] or through reliance on hospital expenses in an older payment model. [20] These measures notably predate contemporary hospital care delivery, which is increasingly dependent on the electronic health record (EHR). To our knowledge, no prior measure of hospital care intensity has been described using the EHR.

Recently, our medical center began an initiative to increase weekend services and staffing to create more uniform availability of care throughout the week. The purpose of this study was to develop a global measure of intensity of care using data derived from the EHR as part of the evaluation of this initiative. [21]

METHODS

We conducted a retrospective analysis of EHR activity for hospital inpatients between January 1, 2011 and December 31, 2011 at New York University Langone Medical Center (NYULMC). During that time period, nearly all inpatient clinical activities at NYULMC were performed and documented through the EHR, Sunrise Clinical Manager (Allscripts, Chicago, IL). These activities include clinical documentation, orders, medication administration, and results of diagnostic tests. Access to the EHR is through Citrix Xenapp Servers (Citrix Systems, Santa Clara, CA), which securely deliver applications from central servers to providers' local terminals.

The primary measure of EHR activity, which we refer to as EHR interactions, was defined as the accessing of a patient's electronic record by a clinician. A provider initiates an interaction by opening a patient's electronic record and concludes it by either opening the record of a different patient or logging out of the EHR. An EHR interaction thus captures a unit of direct patient care, such as documenting a clinical encounter, recording medication administration, or reviewing patient data. Most EHR systems routinely log such interactions to enable compliance departments to audit which users have accessed a patient chart.

The secondary measure of EHR activity was percent central processing unit (CPU), which represents the percent of total available server processing power being used by the Citrix servers at a given time. CPU utilization was averaged over an hour to determine the mean percentage of use for any given hour. As CPU data are not retained for more than 30 days at our institution, we examined CPU usage for the period July 1, 2012 to August 31, 2012.

We evaluated subgroups of EHR interactions by provider type: nurses, resident physicians, attending physicians, pharmacy staff, and all others. We also examined EHR interactions for 2 subgroups of patients: those admitted to the medicine service from the emergency room (ER) and those electively admitted to the surgical service. An elective hospitalization was defined as 1 in which the patient was neither admitted from the ER nor transferred from another hospital. These 2 subgroups were further refined to evaluate EHR interactions among groups of patients admitted during the day, night, weekday, and weeknight. Finally, we examined specific EHR orders that we considered reflective of advancing or altering care, including orders to increase the level of mobilization, to insert or remove a urinary catheter, or to initiate or discontinue antibiotics. As antibiotics are frequently initiated on the day of admission and stopped on the day of discharge, we excluded antibiotic orders that occurred on days of admission or discharge.

RESULTS

During the study period, the mean (standard deviation) number of EHR interactions per patient per hour was 2.49 (1.30). EHR interactions differed by hour and day of the week; the lowest number occurred in early morning on weekends, and the highest occurred around 11:00 _am on weekdays (Figure 1 ). EHR interactions differed among days of the week at all times ( P <0.001), whereas EHR interactions were similar on most hours of Saturday and Sunday as well as Tuesday and Wednesday. At every hour, weekends had a lower number of EHR interactions in comparison to weekdays ( P <0.001). Weekdays showed a substantial increase in the number of EHR interactions between 8:00 _am and 12:00 _pm , followed by a slight decrease in activity between 12:00 _pm and 2:00 _pm , and another increase in activity from 2:00 _pm to 5:00 _pm (Figure 1 ). Weekend days demonstrated marked blunting of this midday peak in intensity. The tracking of an entire month of hospital EHR interactions produced a detailed graphic picture of hospital activity, clearly demarcating rounding hours, lunch hours, weekend days, hospital holidays, and other landmarks (Figure 2 ). The relative rates of census‐adjusted EHR interactions on weekdays versus weekends were 1.76 (95% confidence interval [CI]: 1.74‐1.77) for day, 1.52 (95% CI: 1.50‐1.55) for morning/evening, and 1.14 (95% CI: 1.12‐1.17) for night hours.

Figure 1

Figure 2

Nurses performed the largest number of EHR interactions (39.7%), followed by resident physicians (15.2%), attending physicians (10.2%), and pharmacists (7.6%). The remainder of EHR interactions were performed by other providers (27.4%), whose role in the majority of cases was undefined in the EHR (see Supporting Table 1 in the online version of this article). Daily variation in EHR interactions differed by provider type (Table 1 ). Nurses and resident physicians showed smaller differences in their EHR interactions between weekend and weekdays and among times of day when compared to attending physicians, pharmacy staff, and other staff. EHR interactions showed similar variations to the overall cohort for both medicine patients admitted from the ER and elective surgery patients (Table 1 ). Specific clinical orders designed to sample particularly meaningful interactions, including urinary catheter insertion and removal, patient mobilization orders, and new antibiotic orders, were moderately correlated with total EHR interactions (Table 2 ). In a sensitivity analysis, the comparison of weekday to weekend EHR interactions per daily discharge was similar to the primary analysis, with relative rates of 1.75 (95% CI: 1.73‐1.77), 1.54 (95% CI: 1.50‐1.57), and 1.15 (95% CI: 1.11‐1.18) for day, morning/evening, and night hours, respectively.

As seen in Figure 3 , CPU usage was well correlated with EHR interactions ( r =0.90) and both metrics were lower on weekends as compared to weekdays. A few outliers of increased CPU usage on weekends were observed; these outliers all occurred on Sundays from 12:00 _am to 2:00 _am . The information technology (IT) department at our institution confirmed that these outliers coincided with a weekly virus scan performed at that time.

Figure 3

DISCUSSION

EHR interactions represents a new and accessible measure of hospital care intensity that may be used to track temporal variations in care that are likely to exist in all hospital systems. As the number of hospitals that process and document all clinical activities through the EHR continues to increase, [22, 23] such a measure has the potential to serve as a useful metric in efforts to raise nighttime and weekend care to the same quality as that during weekdays.

We found that EHR interactions differed markedly between days and nights and between weekdays and weekends. A number of prior studies have found temporal variations in clinical outcomes and care. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14] Our study adds to this literature by defining a new measure of the overall intensity of the process of inpatient care. Using this measure, we demonstrate that the increase in midday clinical activity seen during the week is substantially blunted on weekends. This finding adds validity to the designation of both nights and weekends as off hours when examining temporal variations in clinical care. [2, 7]

Other subtle patterns of care delivery emerged throughout the day. For instance, we found a decrease in EHR interactions between 12:00 _pm and 2:00 _pm , likely representing a small lull in clinical activity during the lunchtime hour, whereas EHR interactions were higher in the night and evening hours than in the early morning. The clinical significance of such fluctuations remains undetermined.

Variation throughout the week differed by provider type. Nurses and resident physicians, who are scheduled around the clock, demonstrated the least fluctuation in EHR interaction intensity over time. Attending physicians and other staff showed the greatest variation in weekday versus weekend care.

We defined a second measure of care intensity based on EHR utilization, which we named CPU usage. The advantage of using CPU as a metric is that it easy to measure and track as it is routinely monitored by hospital IT departments as part of regular maintenance. CPU usage can therefore be easily implemented in any institution with an EHR, whereas measuring EHR interactions requires EHR data abstraction and manipulation. The disadvantage of CPU usage as a measure is that it includes nonclinical reporting and other functions and therefore represents a less specific measure of clinical activity. Nonetheless, at our institution, nearly all clinical activities are processed or documented through the EHR, which is maintained on central servers, and CPU usage was well correlated with EHR interactions. We therefore believe that CPU usage represents a useful indicator of hospital clinical activity at a given time.

Several limitations deserve mention. First, EHR interactions may not always reflect actual patient care or clinical documentation. Nonetheless, we also examined specific patient orders and found that variations in these process measures were similar to those in the EHR interaction measure. Second, our methods were developed and evaluated at a single institution and may not be generalizable. Third, increased intensity of care does not necessarily increase quality of care. For instance, laboratory tests are commonly obtained on a daily basis in the hospital, a practice that is costly and often unnecessary. [24] Weekends have been associated with fewer laboratory tests, which may be appropriate as compared to the more frequent testing observed on weekdays. [25] Finally, we do not ascertain whether variations in EHR interactions correlate with clinical outcomes, and believe this to be an area for further research.

In conclusion, EHR interactions represent a new global process measure of care intensity, which was demonstrated to vary over the course of a week. We intend to use this measure at our institution to track progress of an initiative to ensure a high standard of care throughout the course of the week. The extent to which temporal variations in EHR interactions or reductions in these variations are correlated with clinical outcomes deserves further study. We believe this measure, which can be adapted to other institutions, may have a valuable role to play in hospitals' efforts to eliminate excess morbidity and mortality associated with care delivered during nights and weekends.

Hospitals provide acute inpatient care all day and every day. Nonetheless, a number of studies have shown that weekend care may have lower quality than care delivered on weekdays. [1, 2, 3, 4, 5, 6, 7] Weekend care has been associated with increased mortality among patients suffering from a number of conditions [4, 5, 6, 7, 8, 9, 10] and in a number of clinical settings. [11, 12, 13, 14] Findings of poor outcomes on weekends are not universal, though exceptions occur typically in settings where services and clinical staffing are fairly constant throughout the week, such as intensive care units with on‐site intensivists. [15, 16, 17]

These differences in quality and outcomes suggest that there is a difference in intensity of care over the course of the week. Initiatives to address this important safety issue would be strengthened if a shared metric existed to describe the intensity of care provided at a given time of day or day of the week. However, few measures of global hospital intensity of care exist. The metrics that have been developed are limited by measuring only 1 aspect of care delivery, such as weekend nurse staffing, [18] by requiring extensive chart abstraction, [19] or through reliance on hospital expenses in an older payment model. [20] These measures notably predate contemporary hospital care delivery, which is increasingly dependent on the electronic health record (EHR). To our knowledge, no prior measure of hospital care intensity has been described using the EHR.

Recently, our medical center began an initiative to increase weekend services and staffing to create more uniform availability of care throughout the week. The purpose of this study was to develop a global measure of intensity of care using data derived from the EHR as part of the evaluation of this initiative. [21]

METHODS

We conducted a retrospective analysis of EHR activity for hospital inpatients between January 1, 2011 and December 31, 2011 at New York University Langone Medical Center (NYULMC). During that time period, nearly all inpatient clinical activities at NYULMC were performed and documented through the EHR, Sunrise Clinical Manager (Allscripts, Chicago, IL). These activities include clinical documentation, orders, medication administration, and results of diagnostic tests. Access to the EHR is through Citrix Xenapp Servers (Citrix Systems, Santa Clara, CA), which securely deliver applications from central servers to providers' local terminals.

The primary measure of EHR activity, which we refer to as EHR interactions, was defined as the accessing of a patient's electronic record by a clinician. A provider initiates an interaction by opening a patient's electronic record and concludes it by either opening the record of a different patient or logging out of the EHR. An EHR interaction thus captures a unit of direct patient care, such as documenting a clinical encounter, recording medication administration, or reviewing patient data. Most EHR systems routinely log such interactions to enable compliance departments to audit which users have accessed a patient chart.

The secondary measure of EHR activity was percent central processing unit (CPU), which represents the percent of total available server processing power being used by the Citrix servers at a given time. CPU utilization was averaged over an hour to determine the mean percentage of use for any given hour. As CPU data are not retained for more than 30 days at our institution, we examined CPU usage for the period July 1, 2012 to August 31, 2012.

We evaluated subgroups of EHR interactions by provider type: nurses, resident physicians, attending physicians, pharmacy staff, and all others. We also examined EHR interactions for 2 subgroups of patients: those admitted to the medicine service from the emergency room (ER) and those electively admitted to the surgical service. An elective hospitalization was defined as 1 in which the patient was neither admitted from the ER nor transferred from another hospital. These 2 subgroups were further refined to evaluate EHR interactions among groups of patients admitted during the day, night, weekday, and weeknight. Finally, we examined specific EHR orders that we considered reflective of advancing or altering care, including orders to increase the level of mobilization, to insert or remove a urinary catheter, or to initiate or discontinue antibiotics. As antibiotics are frequently initiated on the day of admission and stopped on the day of discharge, we excluded antibiotic orders that occurred on days of admission or discharge.

RESULTS

During the study period, the mean (standard deviation) number of EHR interactions per patient per hour was 2.49 (1.30). EHR interactions differed by hour and day of the week; the lowest number occurred in early morning on weekends, and the highest occurred around 11:00 _am on weekdays (Figure 1 ). EHR interactions differed among days of the week at all times ( P <0.001), whereas EHR interactions were similar on most hours of Saturday and Sunday as well as Tuesday and Wednesday. At every hour, weekends had a lower number of EHR interactions in comparison to weekdays ( P <0.001). Weekdays showed a substantial increase in the number of EHR interactions between 8:00 _am and 12:00 _pm , followed by a slight decrease in activity between 12:00 _pm and 2:00 _pm , and another increase in activity from 2:00 _pm to 5:00 _pm (Figure 1 ). Weekend days demonstrated marked blunting of this midday peak in intensity. The tracking of an entire month of hospital EHR interactions produced a detailed graphic picture of hospital activity, clearly demarcating rounding hours, lunch hours, weekend days, hospital holidays, and other landmarks (Figure 2 ). The relative rates of census‐adjusted EHR interactions on weekdays versus weekends were 1.76 (95% confidence interval [CI]: 1.74‐1.77) for day, 1.52 (95% CI: 1.50‐1.55) for morning/evening, and 1.14 (95% CI: 1.12‐1.17) for night hours.

Figure 1

Figure 2

Nurses performed the largest number of EHR interactions (39.7%), followed by resident physicians (15.2%), attending physicians (10.2%), and pharmacists (7.6%). The remainder of EHR interactions were performed by other providers (27.4%), whose role in the majority of cases was undefined in the EHR (see Supporting Table 1 in the online version of this article). Daily variation in EHR interactions differed by provider type (Table 1 ). Nurses and resident physicians showed smaller differences in their EHR interactions between weekend and weekdays and among times of day when compared to attending physicians, pharmacy staff, and other staff. EHR interactions showed similar variations to the overall cohort for both medicine patients admitted from the ER and elective surgery patients (Table 1 ). Specific clinical orders designed to sample particularly meaningful interactions, including urinary catheter insertion and removal, patient mobilization orders, and new antibiotic orders, were moderately correlated with total EHR interactions (Table 2 ). In a sensitivity analysis, the comparison of weekday to weekend EHR interactions per daily discharge was similar to the primary analysis, with relative rates of 1.75 (95% CI: 1.73‐1.77), 1.54 (95% CI: 1.50‐1.57), and 1.15 (95% CI: 1.11‐1.18) for day, morning/evening, and night hours, respectively.

As seen in Figure 3 , CPU usage was well correlated with EHR interactions ( r =0.90) and both metrics were lower on weekends as compared to weekdays. A few outliers of increased CPU usage on weekends were observed; these outliers all occurred on Sundays from 12:00 _am to 2:00 _am . The information technology (IT) department at our institution confirmed that these outliers coincided with a weekly virus scan performed at that time.

Figure 3

DISCUSSION

EHR interactions represents a new and accessible measure of hospital care intensity that may be used to track temporal variations in care that are likely to exist in all hospital systems. As the number of hospitals that process and document all clinical activities through the EHR continues to increase, [22, 23] such a measure has the potential to serve as a useful metric in efforts to raise nighttime and weekend care to the same quality as that during weekdays.

We found that EHR interactions differed markedly between days and nights and between weekdays and weekends. A number of prior studies have found temporal variations in clinical outcomes and care. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14] Our study adds to this literature by defining a new measure of the overall intensity of the process of inpatient care. Using this measure, we demonstrate that the increase in midday clinical activity seen during the week is substantially blunted on weekends. This finding adds validity to the designation of both nights and weekends as off hours when examining temporal variations in clinical care. [2, 7]

Other subtle patterns of care delivery emerged throughout the day. For instance, we found a decrease in EHR interactions between 12:00 _pm and 2:00 _pm , likely representing a small lull in clinical activity during the lunchtime hour, whereas EHR interactions were higher in the night and evening hours than in the early morning. The clinical significance of such fluctuations remains undetermined.

Variation throughout the week differed by provider type. Nurses and resident physicians, who are scheduled around the clock, demonstrated the least fluctuation in EHR interaction intensity over time. Attending physicians and other staff showed the greatest variation in weekday versus weekend care.

We defined a second measure of care intensity based on EHR utilization, which we named CPU usage. The advantage of using CPU as a metric is that it easy to measure and track as it is routinely monitored by hospital IT departments as part of regular maintenance. CPU usage can therefore be easily implemented in any institution with an EHR, whereas measuring EHR interactions requires EHR data abstraction and manipulation. The disadvantage of CPU usage as a measure is that it includes nonclinical reporting and other functions and therefore represents a less specific measure of clinical activity. Nonetheless, at our institution, nearly all clinical activities are processed or documented through the EHR, which is maintained on central servers, and CPU usage was well correlated with EHR interactions. We therefore believe that CPU usage represents a useful indicator of hospital clinical activity at a given time.

Several limitations deserve mention. First, EHR interactions may not always reflect actual patient care or clinical documentation. Nonetheless, we also examined specific patient orders and found that variations in these process measures were similar to those in the EHR interaction measure. Second, our methods were developed and evaluated at a single institution and may not be generalizable. Third, increased intensity of care does not necessarily increase quality of care. For instance, laboratory tests are commonly obtained on a daily basis in the hospital, a practice that is costly and often unnecessary. [24] Weekends have been associated with fewer laboratory tests, which may be appropriate as compared to the more frequent testing observed on weekdays. [25] Finally, we do not ascertain whether variations in EHR interactions correlate with clinical outcomes, and believe this to be an area for further research.

In conclusion, EHR interactions represent a new global process measure of care intensity, which was demonstrated to vary over the course of a week. We intend to use this measure at our institution to track progress of an initiative to ensure a high standard of care throughout the course of the week. The extent to which temporal variations in EHR interactions or reductions in these variations are correlated with clinical outcomes deserves further study. We believe this measure, which can be adapted to other institutions, may have a valuable role to play in hospitals' efforts to eliminate excess morbidity and mortality associated with care delivered during nights and weekends.

Hospitals provide acute inpatient care all day and every day. Nonetheless, a number of studies have shown that weekend care may have lower quality than care delivered on weekdays. [1, 2, 3, 4, 5, 6, 7] Weekend care has been associated with increased mortality among patients suffering from a number of conditions [4, 5, 6, 7, 8, 9, 10] and in a number of clinical settings. [11, 12, 13, 14] Findings of poor outcomes on weekends are not universal, though exceptions occur typically in settings where services and clinical staffing are fairly constant throughout the week, such as intensive care units with on‐site intensivists. [15, 16, 17]

These differences in quality and outcomes suggest that there is a difference in intensity of care over the course of the week. Initiatives to address this important safety issue would be strengthened if a shared metric existed to describe the intensity of care provided at a given time of day or day of the week. However, few measures of global hospital intensity of care exist. The metrics that have been developed are limited by measuring only 1 aspect of care delivery, such as weekend nurse staffing, [18] by requiring extensive chart abstraction, [19] or through reliance on hospital expenses in an older payment model. [20] These measures notably predate contemporary hospital care delivery, which is increasingly dependent on the electronic health record (EHR). To our knowledge, no prior measure of hospital care intensity has been described using the EHR.

Recently, our medical center began an initiative to increase weekend services and staffing to create more uniform availability of care throughout the week. The purpose of this study was to develop a global measure of intensity of care using data derived from the EHR as part of the evaluation of this initiative. [21]

METHODS

We conducted a retrospective analysis of EHR activity for hospital inpatients between January 1, 2011 and December 31, 2011 at New York University Langone Medical Center (NYULMC). During that time period, nearly all inpatient clinical activities at NYULMC were performed and documented through the EHR, Sunrise Clinical Manager (Allscripts, Chicago, IL). These activities include clinical documentation, orders, medication administration, and results of diagnostic tests. Access to the EHR is through Citrix Xenapp Servers (Citrix Systems, Santa Clara, CA), which securely deliver applications from central servers to providers' local terminals.

The primary measure of EHR activity, which we refer to as EHR interactions, was defined as the accessing of a patient's electronic record by a clinician. A provider initiates an interaction by opening a patient's electronic record and concludes it by either opening the record of a different patient or logging out of the EHR. An EHR interaction thus captures a unit of direct patient care, such as documenting a clinical encounter, recording medication administration, or reviewing patient data. Most EHR systems routinely log such interactions to enable compliance departments to audit which users have accessed a patient chart.

The secondary measure of EHR activity was percent central processing unit (CPU), which represents the percent of total available server processing power being used by the Citrix servers at a given time. CPU utilization was averaged over an hour to determine the mean percentage of use for any given hour. As CPU data are not retained for more than 30 days at our institution, we examined CPU usage for the period July 1, 2012 to August 31, 2012.

We evaluated subgroups of EHR interactions by provider type: nurses, resident physicians, attending physicians, pharmacy staff, and all others. We also examined EHR interactions for 2 subgroups of patients: those admitted to the medicine service from the emergency room (ER) and those electively admitted to the surgical service. An elective hospitalization was defined as 1 in which the patient was neither admitted from the ER nor transferred from another hospital. These 2 subgroups were further refined to evaluate EHR interactions among groups of patients admitted during the day, night, weekday, and weeknight. Finally, we examined specific EHR orders that we considered reflective of advancing or altering care, including orders to increase the level of mobilization, to insert or remove a urinary catheter, or to initiate or discontinue antibiotics. As antibiotics are frequently initiated on the day of admission and stopped on the day of discharge, we excluded antibiotic orders that occurred on days of admission or discharge.

RESULTS

During the study period, the mean (standard deviation) number of EHR interactions per patient per hour was 2.49 (1.30). EHR interactions differed by hour and day of the week; the lowest number occurred in early morning on weekends, and the highest occurred around 11:00 _am on weekdays (Figure 1 ). EHR interactions differed among days of the week at all times ( P <0.001), whereas EHR interactions were similar on most hours of Saturday and Sunday as well as Tuesday and Wednesday. At every hour, weekends had a lower number of EHR interactions in comparison to weekdays ( P <0.001). Weekdays showed a substantial increase in the number of EHR interactions between 8:00 _am and 12:00 _pm , followed by a slight decrease in activity between 12:00 _pm and 2:00 _pm , and another increase in activity from 2:00 _pm to 5:00 _pm (Figure 1 ). Weekend days demonstrated marked blunting of this midday peak in intensity. The tracking of an entire month of hospital EHR interactions produced a detailed graphic picture of hospital activity, clearly demarcating rounding hours, lunch hours, weekend days, hospital holidays, and other landmarks (Figure 2 ). The relative rates of census‐adjusted EHR interactions on weekdays versus weekends were 1.76 (95% confidence interval [CI]: 1.74‐1.77) for day, 1.52 (95% CI: 1.50‐1.55) for morning/evening, and 1.14 (95% CI: 1.12‐1.17) for night hours.

Figure 1

Figure 2

Nurses performed the largest number of EHR interactions (39.7%), followed by resident physicians (15.2%), attending physicians (10.2%), and pharmacists (7.6%). The remainder of EHR interactions were performed by other providers (27.4%), whose role in the majority of cases was undefined in the EHR (see Supporting Table 1 in the online version of this article). Daily variation in EHR interactions differed by provider type (Table 1 ). Nurses and resident physicians showed smaller differences in their EHR interactions between weekend and weekdays and among times of day when compared to attending physicians, pharmacy staff, and other staff. EHR interactions showed similar variations to the overall cohort for both medicine patients admitted from the ER and elective surgery patients (Table 1 ). Specific clinical orders designed to sample particularly meaningful interactions, including urinary catheter insertion and removal, patient mobilization orders, and new antibiotic orders, were moderately correlated with total EHR interactions (Table 2 ). In a sensitivity analysis, the comparison of weekday to weekend EHR interactions per daily discharge was similar to the primary analysis, with relative rates of 1.75 (95% CI: 1.73‐1.77), 1.54 (95% CI: 1.50‐1.57), and 1.15 (95% CI: 1.11‐1.18) for day, morning/evening, and night hours, respectively.

As seen in Figure 3 , CPU usage was well correlated with EHR interactions ( r =0.90) and both metrics were lower on weekends as compared to weekdays. A few outliers of increased CPU usage on weekends were observed; these outliers all occurred on Sundays from 12:00 _am to 2:00 _am . The information technology (IT) department at our institution confirmed that these outliers coincided with a weekly virus scan performed at that time.

Figure 3

DISCUSSION

EHR interactions represents a new and accessible measure of hospital care intensity that may be used to track temporal variations in care that are likely to exist in all hospital systems. As the number of hospitals that process and document all clinical activities through the EHR continues to increase, [22, 23] such a measure has the potential to serve as a useful metric in efforts to raise nighttime and weekend care to the same quality as that during weekdays.

We found that EHR interactions differed markedly between days and nights and between weekdays and weekends. A number of prior studies have found temporal variations in clinical outcomes and care. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14] Our study adds to this literature by defining a new measure of the overall intensity of the process of inpatient care. Using this measure, we demonstrate that the increase in midday clinical activity seen during the week is substantially blunted on weekends. This finding adds validity to the designation of both nights and weekends as off hours when examining temporal variations in clinical care. [2, 7]

Other subtle patterns of care delivery emerged throughout the day. For instance, we found a decrease in EHR interactions between 12:00 _pm and 2:00 _pm , likely representing a small lull in clinical activity during the lunchtime hour, whereas EHR interactions were higher in the night and evening hours than in the early morning. The clinical significance of such fluctuations remains undetermined.

Variation throughout the week differed by provider type. Nurses and resident physicians, who are scheduled around the clock, demonstrated the least fluctuation in EHR interaction intensity over time. Attending physicians and other staff showed the greatest variation in weekday versus weekend care.

We defined a second measure of care intensity based on EHR utilization, which we named CPU usage. The advantage of using CPU as a metric is that it easy to measure and track as it is routinely monitored by hospital IT departments as part of regular maintenance. CPU usage can therefore be easily implemented in any institution with an EHR, whereas measuring EHR interactions requires EHR data abstraction and manipulation. The disadvantage of CPU usage as a measure is that it includes nonclinical reporting and other functions and therefore represents a less specific measure of clinical activity. Nonetheless, at our institution, nearly all clinical activities are processed or documented through the EHR, which is maintained on central servers, and CPU usage was well correlated with EHR interactions. We therefore believe that CPU usage represents a useful indicator of hospital clinical activity at a given time.

Several limitations deserve mention. First, EHR interactions may not always reflect actual patient care or clinical documentation. Nonetheless, we also examined specific patient orders and found that variations in these process measures were similar to those in the EHR interaction measure. Second, our methods were developed and evaluated at a single institution and may not be generalizable. Third, increased intensity of care does not necessarily increase quality of care. For instance, laboratory tests are commonly obtained on a daily basis in the hospital, a practice that is costly and often unnecessary. [24] Weekends have been associated with fewer laboratory tests, which may be appropriate as compared to the more frequent testing observed on weekdays. [25] Finally, we do not ascertain whether variations in EHR interactions correlate with clinical outcomes, and believe this to be an area for further research.

In conclusion, EHR interactions represent a new global process measure of care intensity, which was demonstrated to vary over the course of a week. We intend to use this measure at our institution to track progress of an initiative to ensure a high standard of care throughout the course of the week. The extent to which temporal variations in EHR interactions or reductions in these variations are correlated with clinical outcomes deserves further study. We believe this measure, which can be adapted to other institutions, may have a valuable role to play in hospitals' efforts to eliminate excess morbidity and mortality associated with care delivered during nights and weekends.

Mental illness is highly prevalent, with approximately 30% of the US population meeting criteria for at least 1 disorder.[1] In the medically ill population, psychiatric disease is even more common; a 2005 survey showed that half of all patients visiting primary care physicians met criteria for a mental disorder.[2] Conversely, those with serious mental illness suffer greater medical morbidity than the general population, with higher rates of obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, human immunodeficiency virus, viral hepatitis, and tuberculosis.[3] When acute medical problems arise, those with mental illness endure longer hospitalizations; the presence of a psychiatric disturbance in the general medical setting has been shown to be a robust predictor of increased hospital length of stay.[4, 5]

Because of the strong correlation between medical and mental illness, hospitalists will care for patients with psychiatric disorders. Despite this, internists generally receive a paucity of formal training in the treatment of mental disturbances. One survey of university‐affiliated internal medicine residencies revealed that only 10% of programs offered any kind of modest curriculum in psychiatric education.[6] Regardless of this lack of preparation, hospitalists are called upon at each admission to make decisions that affect the psychiatric treatment of patients on psychotropic medication; namely, they must decide whether to continue or discontinue psychiatric medications. Many physicians reflexively discontinue a patient's chronic medications upon admission to the hospital; one study reported an adjusted odds ratio of between 1.18 and 1.86 for stopping a medication prescribed for a chronic condition.[7]

This review aims to assist the hospitalist in making an informed decision about the continuation of psychotropic medications in the medically ill patient. First, it examines the risks of stopping psychotropic medication, including psychiatric decompensation and discontinuation syndromes. It also explores the challenges of medication continuation in the context of changing pharmacokinetics and emerging side effects. Ultimately, physicians and patients must make collaborative decisions, weighing the risk of medication interactions against the potential adverse effects of psychiatric decompensation.

DISCONTINUATION

DRUG‐SPECIFIC DISCONTINUATION SYNDROMES

CONTINUATION

Reflexive discontinuation of psychotropic medications can clearly lead to adverse outcomes. However, when hospitalists decide to continue a patient's psychotropic medications, they must also be cognizant of potential complications. Modifications may be necessary because of hepatic, renal, or cardiac disease. In addition, physicians need to be aware of drug‐drug interactions. Pharmacotherapy for medically ill elderly patients may require dose modifications to account for an increased lipophilic volume of distribution and a decreased rate of metabolism.[33] Finally, pregnancy can present additional challenges regarding dose modifications and teratogenicity.

On the other hand, hospitalists must be aware that continuing a patient's psychotropic medication may not be the cause of new psychiatric symptoms. Drugs prescribed for medical disorders (eg, corticosteroids) often cause psychiatric symptoms. In addition, psychiatric symptoms may emerge at times of nonpsychotropic medication withdrawal or due to nonpsychotropic drug‐drug interactions.[4] Groups of medications commonly associated with psychiatric disturbances include analgesics, sedatives, anesthetics, anticonvulsants, and anticholinergics.

PHARMACOKINETICS: PSYCHOTROPIC TOXICITY

Medical illness alters the body's steady state, and renal or hepatic metabolism may be impaired when a patient requires hospitalization. Additionally, new medications may increase the effects of psychotropics, whether by intrinsic augmentation of effect or decreased psychotropic clearance. Ultimately, these changes can lead to psychotropic toxicity.

Specific toxicities merit discussion. First, serotonin syndrome is a potentially fatal condition. The majority of cases occur with synergistic serotonergic medication administration, though there are case reports of the syndrome occurring with addition of inhibitors of cytochrome p450 2D6 and/or 3A4 to SSRIs. A large number of medications from different classes have been indicated (Table 2).[34] Symptoms generally occur within 24 hours of medication administration and include mental status changes, autonomic instability, and neuromuscular hyperactivity. When serotonin syndrome is suspected, the offending agent should be discontinued immediately. There is no definitive treatment, though supportive care can be lifesaving.[34]

In addition to serotonin syndrome, hypertensive emergency may occur due to drug interactions with MAOIs. MAOIs inhibit the enzyme monoamine oxidase, resulting in elevated levels of serotonin, histamine, and catecholamines in the blood. Coadministration of MAOIs and sympathomimetic agents (such as cough suppressants and analgesics) may dangerously increase adrenergic stimulation, elevating blood pressure to the point of end‐organ damage. Please see Table 3 for a full list of drugs indicated in MAOI‐associated hypertensive crisis.[35] To ensure safety, it is recommended that MAOIs be discontinued for 14 days prior to introducing medications with sympathomimetic properties, and vice versa. Because of its longer half‐life, a 5‐week washout period is recommended for fluoxetine.[35]

Lithium toxicity may result from changing patient pharmacokinetics. Lithium is almost entirely renally excreted, and acute kidney injury may precipitously raise serum levels. Within the renal collecting system, lithium is handled similarly to sodium, with 80% reabsorbed from the proximal tubule to the collecting duct. Thus, factors that decrease glomerular filtration rate (GFR) and increase proximal tubule absorption will increase serum lithium levels. For example, decreased effective arterial volume (due to dehydration, cirrhosis, nephrotic syndrome, or heart failure) may elevate lithium levels. Additionally, medications that decrease GFR may increase lithium reabsorption. These include nonsteroidal anti‐inflammatory drugs, angiotensin‐converting enzyme inhibitors, and thiazide diuretics. Because of lithium's narrow therapeutic index, small elevations in serum levels can lead to toxicity. Severity of intoxication correlates with serum concentration. Symptoms range from lethargy, weakness, tremor, ataxia, and gastrointestinal distress to coma, seizures, renal failure, and death. Toxicity is also associated with electrocardiograph (ECG) changes, including ST‐segment depression and T‐wave inversion in the lateral precordial leads. Sinus node dysfunction can also occur. Definitive treatment for lithium toxicity is hemodialysis.[36]

Though the therapeutic index is much wider for valproic acid than for lithium, valproate toxicity may also occur in the medically ill patient with previously stable serum levels. Valproic acid is highly protein‐bound at therapeutic levels, and is metabolized largely through hepatic glucuronidation. Initiation of medications that compete for protein‐binding sites, including aspirin, has led to valproate toxicity. Moreover, acute liver failure or addition of drugs that compete with hepatic microsomal enzymes may lead to decreased excretion of valproic acid. Poisoning may result in central nervous system (CNS) and respiratory depression, hypotension, cerebral edema, and pancreatitis. True hepatoxicity is rare, though hyperammonemia is widely documented. Thrombocytopenia is the most common hematologic abnormality associated with overdose. However, thrombocytopenia may also occur without complication in patients on stable therapeutic doses. Treatment is largely supportive, though hemoperfusion and hemodialysis may be used when serum levels are >300 g/mL, as only 35% of the drug is protein‐bound at that level. Naloxone has been shown in case reports to reverse valproic acid‐induced coma, and L‐carnitine has been increasingly recommended for hyperammonemia.[37, 38]

PHARMACOKINETICS: DRUG‐DRUG INTERACTIONS

As discussed above, the addition of a new medication can increase previously stable levels of psychotropic drugs, leading to toxicity. Conversely, mental health medications can alter the expected metabolism of a drug being used to treat acute medical illness. Many psychotropics are metabolized via the cytochrome p450 enzyme, particularly the SSRIs (Table 4).[39] A number of antimicrobial and antiarrythmic medications are also cleared via this route, leading to potential toxic or subtherapeutic levels when drug‐drug interactions occur.

PSYCHOTROPIC ADVERSE EFFECTS

Psychotropic medications may also cause side effects that contribute to the clinical presentation, requiring ongoing monitoring, a dose reduction, or psychotropic discontinuation. Potential adverse effects that commonly impact psychopharmacologic management include anticholinergic side effects, cardiac effects, and sedation.

ANTICHOLINERGIC EFFECTS AND TOXICITY

Newly emerging anticholinergic effects may be particularly troubling. Dry mouth may cause swallowing difficulty and aspiration. Pupillary dilatation and dry eyes can increase risk of falls. Constipation may evolve into fecal impaction, and urinary retention can contribute to increased catheter use and infection. CNS effects are perhaps the most serious, ranging from drowsiness and memory impairment to frank delirium.[40]

Many psychotropic drugs are anti cholinergic. Among the antidepressants, the TCAs and paroxetine have the highest anticholinergic activity. Anticholinergic effects have also been reported with the low potency first generation neuroleptics and with the atypical antipsychotics olanzapine and clozapine. Additionally, medications used to treat the extrapyramidal symptoms associated with antipsychotics (such as benztropine and diphenhydramine) are strongly anticholinergic.[41] Patients without previous overt anticholinergic symptoms from these medications may experience adverse effects when hospitalized. Medical illness or new medications may alter psychotropic drug metabolism and elimination, leading to accumulation of their anticholinergic effects. Many medications used in the hospital also have intrinsic anticholinergic activity. These include some antiemetics, antispasmodics, antiarrhythmics, and histamine H2 receptor blockers. Elderly patients are particularly prone to anticholinergic effects due to age‐related deficits in cholinergic transmission.[40]

QTc PROLONGATION

QTc prolongation is a potentially lethal side effect of certain medications. Prolonged QTc increases the risk of cardiac mortality and sudden death, presumably related to onset of torsades de pointe. Certain antidepressants have consistently been associated with QTc prolongation, particularly the TCAs. In addition, the US Food and Drug Administration recently issued the recommendation that the SSRI citalopram not be used at doses >40 mg (and 20 mg in those with hepatic impairment or age >60 years) due to results of a randomized controlled trial that showed a dose‐response increase in QTc. Antipsychotic medications have also been shown to increase QTc, with the greatest evidence for thioridazine and the first‐generation, low‐potency neuroleptics. Haloperidol (particularly the intravenous formulation) has also been linked to both long QTc and torsades, though data may be confounded by the degree of medical illness of patients receiving the medication.[42] Of the atypicals, ziprasidone causes the greatest QTc prolongation.[43] However, a large retrospective cohort study showed similar risk increase of sudden cardiac death (2‐fold) among all antipsychotics (including typicals and atypicals) when examined individually.[44]

Additional risk factors for QTc prolongation abound in the hospitalized patient. These include many medical problems, including electrolyte abnormalities, heart conditions, renal and hepatic dysfunction, and CNS injury. Hospitalized patients are also exposed to the cumulative effects of medications that increase duration of QTc, such as class I and class III antiarrhythmics. Additionally, certain antimicrobials, including macrolide antibiotics and antifungals, have been associated with QTc prolongation via pharmacokinetic interactions.

Because of this, QTc should be measured upon admission in patients on stable doses of psychotropics that predispose to prolongation. Addition of other medications known to contribute to increased QTc should prompt further ECGs. Electrolytes, particularly potassium and magnesium, should be aggressively repleted. When QTc extends beyond 500 ms, consideration should be given to discontinuing or changing medications that can contribute to QTc prolongation (whether psychotropics or drugs used to treat acute medical problems).[42]

SEDATION

Sedation is another potential side effect of psychotropic medications. Although sedation is beneficial for agitation and anxiety, sedated patients may be unable to participate in treatment. They are also at greater risk of aspiration and falls.

Antipsychotics cause sedation through antagonism of 1 adrenergic and H1 histaminergic receptors. Effects are most pronounced with the low‐potency, first‐generation antipsychotics and the atypicals quetiapine and clozapine. Some antidepressants, including the TCAs and mirtazapine, also cause somnolence by histamine H1‐receptor antagonism. If a patient has been psychiatrically stable on a particular antipsychotic or antidepressant, but has psychotropic‐induced sedation that interferes with treatment, hospitalists may want to consider temporarily decreasing the dose.

Benzodiazepines induce sedation by increasing ‐aminobutyric acid‐ergic transmission. There is significant overlap between anxiolytic and sedating doses of benzodiazepines. The amount of sedation is related to dose, speed of absorption, and onset of CNS penetration. Thus, sedation may be minimized by using a lower dose or switching to an equivalent dose of a slower‐onset benzodiazepine.[45, 46]

CONCLUSION

The decision to continue or discontinue psychotropic medications is often challenging. It requires the hospitalist to carefully weigh the risks and benefits of the ongoing treatment versus discontinuation, while also considering the patient's preference whenever possible. Sudden cessation of psychotropics can lead to a number of unwanted complications, from mild withdrawal to life‐threatening autonomic instability and psychiatric decompensation. Yet psychotropic continuation can also lead to unwanted drug‐drug interactions and newly emergent side effects.

To improve patient safety and outcomes, hospitalists must take a cautious and well‐thought out approach to treating patients on psychotropic drugs. Reflexive cessation of home medications must be avoided. If hepatic or renal insufficiency develops, medication doses may need to be adjusted. When available, drug levels should guide dose adjustments. If side effects occur, the patient's medication list should be carefully reviewed for potential drug‐drug interactions. Maintaining mental health may mean substituting another drug for one that interferes with home psychotropic medications. Psychotropic doses may also be minimized to decrease side effects. When a psychotropic must be discontinued, tapering is recommended over an abrupt discontinuation, except in the case of an acute toxicity. Moreover, cross‐titration to another effective agent may prevent psychiatric decompensation.

Additionally, hospitalists should use all available resources when deciding on a patient's psychotropic regimen. Mobile devices and online resources can assist with pharmacokinetics. Pharmacists can help with more complex questions or potential drug substitutions. Consultation‐liaison psychiatrists can be a valuable resource in ensuring the safety and stability of a patient with psychiatric comorbidity within the medical environment. The consultant may assist by assessing a patient's current psychiatric state and recommending psychotropic medication changes when needed.

Mental illness is highly prevalent, with approximately 30% of the US population meeting criteria for at least 1 disorder.[1] In the medically ill population, psychiatric disease is even more common; a 2005 survey showed that half of all patients visiting primary care physicians met criteria for a mental disorder.[2] Conversely, those with serious mental illness suffer greater medical morbidity than the general population, with higher rates of obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, human immunodeficiency virus, viral hepatitis, and tuberculosis.[3] When acute medical problems arise, those with mental illness endure longer hospitalizations; the presence of a psychiatric disturbance in the general medical setting has been shown to be a robust predictor of increased hospital length of stay.[4, 5]

Because of the strong correlation between medical and mental illness, hospitalists will care for patients with psychiatric disorders. Despite this, internists generally receive a paucity of formal training in the treatment of mental disturbances. One survey of university‐affiliated internal medicine residencies revealed that only 10% of programs offered any kind of modest curriculum in psychiatric education.[6] Regardless of this lack of preparation, hospitalists are called upon at each admission to make decisions that affect the psychiatric treatment of patients on psychotropic medication; namely, they must decide whether to continue or discontinue psychiatric medications. Many physicians reflexively discontinue a patient's chronic medications upon admission to the hospital; one study reported an adjusted odds ratio of between 1.18 and 1.86 for stopping a medication prescribed for a chronic condition.[7]

This review aims to assist the hospitalist in making an informed decision about the continuation of psychotropic medications in the medically ill patient. First, it examines the risks of stopping psychotropic medication, including psychiatric decompensation and discontinuation syndromes. It also explores the challenges of medication continuation in the context of changing pharmacokinetics and emerging side effects. Ultimately, physicians and patients must make collaborative decisions, weighing the risk of medication interactions against the potential adverse effects of psychiatric decompensation.

DISCONTINUATION

DRUG‐SPECIFIC DISCONTINUATION SYNDROMES

CONTINUATION

Reflexive discontinuation of psychotropic medications can clearly lead to adverse outcomes. However, when hospitalists decide to continue a patient's psychotropic medications, they must also be cognizant of potential complications. Modifications may be necessary because of hepatic, renal, or cardiac disease. In addition, physicians need to be aware of drug‐drug interactions. Pharmacotherapy for medically ill elderly patients may require dose modifications to account for an increased lipophilic volume of distribution and a decreased rate of metabolism.[33] Finally, pregnancy can present additional challenges regarding dose modifications and teratogenicity.

On the other hand, hospitalists must be aware that continuing a patient's psychotropic medication may not be the cause of new psychiatric symptoms. Drugs prescribed for medical disorders (eg, corticosteroids) often cause psychiatric symptoms. In addition, psychiatric symptoms may emerge at times of nonpsychotropic medication withdrawal or due to nonpsychotropic drug‐drug interactions.[4] Groups of medications commonly associated with psychiatric disturbances include analgesics, sedatives, anesthetics, anticonvulsants, and anticholinergics.

PHARMACOKINETICS: PSYCHOTROPIC TOXICITY

Medical illness alters the body's steady state, and renal or hepatic metabolism may be impaired when a patient requires hospitalization. Additionally, new medications may increase the effects of psychotropics, whether by intrinsic augmentation of effect or decreased psychotropic clearance. Ultimately, these changes can lead to psychotropic toxicity.

Specific toxicities merit discussion. First, serotonin syndrome is a potentially fatal condition. The majority of cases occur with synergistic serotonergic medication administration, though there are case reports of the syndrome occurring with addition of inhibitors of cytochrome p450 2D6 and/or 3A4 to SSRIs. A large number of medications from different classes have been indicated (Table 2).[34] Symptoms generally occur within 24 hours of medication administration and include mental status changes, autonomic instability, and neuromuscular hyperactivity. When serotonin syndrome is suspected, the offending agent should be discontinued immediately. There is no definitive treatment, though supportive care can be lifesaving.[34]

In addition to serotonin syndrome, hypertensive emergency may occur due to drug interactions with MAOIs. MAOIs inhibit the enzyme monoamine oxidase, resulting in elevated levels of serotonin, histamine, and catecholamines in the blood. Coadministration of MAOIs and sympathomimetic agents (such as cough suppressants and analgesics) may dangerously increase adrenergic stimulation, elevating blood pressure to the point of end‐organ damage. Please see Table 3 for a full list of drugs indicated in MAOI‐associated hypertensive crisis.[35] To ensure safety, it is recommended that MAOIs be discontinued for 14 days prior to introducing medications with sympathomimetic properties, and vice versa. Because of its longer half‐life, a 5‐week washout period is recommended for fluoxetine.[35]

Lithium toxicity may result from changing patient pharmacokinetics. Lithium is almost entirely renally excreted, and acute kidney injury may precipitously raise serum levels. Within the renal collecting system, lithium is handled similarly to sodium, with 80% reabsorbed from the proximal tubule to the collecting duct. Thus, factors that decrease glomerular filtration rate (GFR) and increase proximal tubule absorption will increase serum lithium levels. For example, decreased effective arterial volume (due to dehydration, cirrhosis, nephrotic syndrome, or heart failure) may elevate lithium levels. Additionally, medications that decrease GFR may increase lithium reabsorption. These include nonsteroidal anti‐inflammatory drugs, angiotensin‐converting enzyme inhibitors, and thiazide diuretics. Because of lithium's narrow therapeutic index, small elevations in serum levels can lead to toxicity. Severity of intoxication correlates with serum concentration. Symptoms range from lethargy, weakness, tremor, ataxia, and gastrointestinal distress to coma, seizures, renal failure, and death. Toxicity is also associated with electrocardiograph (ECG) changes, including ST‐segment depression and T‐wave inversion in the lateral precordial leads. Sinus node dysfunction can also occur. Definitive treatment for lithium toxicity is hemodialysis.[36]

Though the therapeutic index is much wider for valproic acid than for lithium, valproate toxicity may also occur in the medically ill patient with previously stable serum levels. Valproic acid is highly protein‐bound at therapeutic levels, and is metabolized largely through hepatic glucuronidation. Initiation of medications that compete for protein‐binding sites, including aspirin, has led to valproate toxicity. Moreover, acute liver failure or addition of drugs that compete with hepatic microsomal enzymes may lead to decreased excretion of valproic acid. Poisoning may result in central nervous system (CNS) and respiratory depression, hypotension, cerebral edema, and pancreatitis. True hepatoxicity is rare, though hyperammonemia is widely documented. Thrombocytopenia is the most common hematologic abnormality associated with overdose. However, thrombocytopenia may also occur without complication in patients on stable therapeutic doses. Treatment is largely supportive, though hemoperfusion and hemodialysis may be used when serum levels are >300 g/mL, as only 35% of the drug is protein‐bound at that level. Naloxone has been shown in case reports to reverse valproic acid‐induced coma, and L‐carnitine has been increasingly recommended for hyperammonemia.[37, 38]

PHARMACOKINETICS: DRUG‐DRUG INTERACTIONS

As discussed above, the addition of a new medication can increase previously stable levels of psychotropic drugs, leading to toxicity. Conversely, mental health medications can alter the expected metabolism of a drug being used to treat acute medical illness. Many psychotropics are metabolized via the cytochrome p450 enzyme, particularly the SSRIs (Table 4).[39] A number of antimicrobial and antiarrythmic medications are also cleared via this route, leading to potential toxic or subtherapeutic levels when drug‐drug interactions occur.

PSYCHOTROPIC ADVERSE EFFECTS

Psychotropic medications may also cause side effects that contribute to the clinical presentation, requiring ongoing monitoring, a dose reduction, or psychotropic discontinuation. Potential adverse effects that commonly impact psychopharmacologic management include anticholinergic side effects, cardiac effects, and sedation.

ANTICHOLINERGIC EFFECTS AND TOXICITY

Newly emerging anticholinergic effects may be particularly troubling. Dry mouth may cause swallowing difficulty and aspiration. Pupillary dilatation and dry eyes can increase risk of falls. Constipation may evolve into fecal impaction, and urinary retention can contribute to increased catheter use and infection. CNS effects are perhaps the most serious, ranging from drowsiness and memory impairment to frank delirium.[40]

Many psychotropic drugs are anti cholinergic. Among the antidepressants, the TCAs and paroxetine have the highest anticholinergic activity. Anticholinergic effects have also been reported with the low potency first generation neuroleptics and with the atypical antipsychotics olanzapine and clozapine. Additionally, medications used to treat the extrapyramidal symptoms associated with antipsychotics (such as benztropine and diphenhydramine) are strongly anticholinergic.[41] Patients without previous overt anticholinergic symptoms from these medications may experience adverse effects when hospitalized. Medical illness or new medications may alter psychotropic drug metabolism and elimination, leading to accumulation of their anticholinergic effects. Many medications used in the hospital also have intrinsic anticholinergic activity. These include some antiemetics, antispasmodics, antiarrhythmics, and histamine H2 receptor blockers. Elderly patients are particularly prone to anticholinergic effects due to age‐related deficits in cholinergic transmission.[40]

QTc PROLONGATION

QTc prolongation is a potentially lethal side effect of certain medications. Prolonged QTc increases the risk of cardiac mortality and sudden death, presumably related to onset of torsades de pointe. Certain antidepressants have consistently been associated with QTc prolongation, particularly the TCAs. In addition, the US Food and Drug Administration recently issued the recommendation that the SSRI citalopram not be used at doses >40 mg (and 20 mg in those with hepatic impairment or age >60 years) due to results of a randomized controlled trial that showed a dose‐response increase in QTc. Antipsychotic medications have also been shown to increase QTc, with the greatest evidence for thioridazine and the first‐generation, low‐potency neuroleptics. Haloperidol (particularly the intravenous formulation) has also been linked to both long QTc and torsades, though data may be confounded by the degree of medical illness of patients receiving the medication.[42] Of the atypicals, ziprasidone causes the greatest QTc prolongation.[43] However, a large retrospective cohort study showed similar risk increase of sudden cardiac death (2‐fold) among all antipsychotics (including typicals and atypicals) when examined individually.[44]

Additional risk factors for QTc prolongation abound in the hospitalized patient. These include many medical problems, including electrolyte abnormalities, heart conditions, renal and hepatic dysfunction, and CNS injury. Hospitalized patients are also exposed to the cumulative effects of medications that increase duration of QTc, such as class I and class III antiarrhythmics. Additionally, certain antimicrobials, including macrolide antibiotics and antifungals, have been associated with QTc prolongation via pharmacokinetic interactions.

Because of this, QTc should be measured upon admission in patients on stable doses of psychotropics that predispose to prolongation. Addition of other medications known to contribute to increased QTc should prompt further ECGs. Electrolytes, particularly potassium and magnesium, should be aggressively repleted. When QTc extends beyond 500 ms, consideration should be given to discontinuing or changing medications that can contribute to QTc prolongation (whether psychotropics or drugs used to treat acute medical problems).[42]

SEDATION

Sedation is another potential side effect of psychotropic medications. Although sedation is beneficial for agitation and anxiety, sedated patients may be unable to participate in treatment. They are also at greater risk of aspiration and falls.

Antipsychotics cause sedation through antagonism of 1 adrenergic and H1 histaminergic receptors. Effects are most pronounced with the low‐potency, first‐generation antipsychotics and the atypicals quetiapine and clozapine. Some antidepressants, including the TCAs and mirtazapine, also cause somnolence by histamine H1‐receptor antagonism. If a patient has been psychiatrically stable on a particular antipsychotic or antidepressant, but has psychotropic‐induced sedation that interferes with treatment, hospitalists may want to consider temporarily decreasing the dose.

Benzodiazepines induce sedation by increasing ‐aminobutyric acid‐ergic transmission. There is significant overlap between anxiolytic and sedating doses of benzodiazepines. The amount of sedation is related to dose, speed of absorption, and onset of CNS penetration. Thus, sedation may be minimized by using a lower dose or switching to an equivalent dose of a slower‐onset benzodiazepine.[45, 46]

CONCLUSION

The decision to continue or discontinue psychotropic medications is often challenging. It requires the hospitalist to carefully weigh the risks and benefits of the ongoing treatment versus discontinuation, while also considering the patient's preference whenever possible. Sudden cessation of psychotropics can lead to a number of unwanted complications, from mild withdrawal to life‐threatening autonomic instability and psychiatric decompensation. Yet psychotropic continuation can also lead to unwanted drug‐drug interactions and newly emergent side effects.

To improve patient safety and outcomes, hospitalists must take a cautious and well‐thought out approach to treating patients on psychotropic drugs. Reflexive cessation of home medications must be avoided. If hepatic or renal insufficiency develops, medication doses may need to be adjusted. When available, drug levels should guide dose adjustments. If side effects occur, the patient's medication list should be carefully reviewed for potential drug‐drug interactions. Maintaining mental health may mean substituting another drug for one that interferes with home psychotropic medications. Psychotropic doses may also be minimized to decrease side effects. When a psychotropic must be discontinued, tapering is recommended over an abrupt discontinuation, except in the case of an acute toxicity. Moreover, cross‐titration to another effective agent may prevent psychiatric decompensation.

Additionally, hospitalists should use all available resources when deciding on a patient's psychotropic regimen. Mobile devices and online resources can assist with pharmacokinetics. Pharmacists can help with more complex questions or potential drug substitutions. Consultation‐liaison psychiatrists can be a valuable resource in ensuring the safety and stability of a patient with psychiatric comorbidity within the medical environment. The consultant may assist by assessing a patient's current psychiatric state and recommending psychotropic medication changes when needed.

Mental illness is highly prevalent, with approximately 30% of the US population meeting criteria for at least 1 disorder.[1] In the medically ill population, psychiatric disease is even more common; a 2005 survey showed that half of all patients visiting primary care physicians met criteria for a mental disorder.[2] Conversely, those with serious mental illness suffer greater medical morbidity than the general population, with higher rates of obesity, diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease, human immunodeficiency virus, viral hepatitis, and tuberculosis.[3] When acute medical problems arise, those with mental illness endure longer hospitalizations; the presence of a psychiatric disturbance in the general medical setting has been shown to be a robust predictor of increased hospital length of stay.[4, 5]

Because of the strong correlation between medical and mental illness, hospitalists will care for patients with psychiatric disorders. Despite this, internists generally receive a paucity of formal training in the treatment of mental disturbances. One survey of university‐affiliated internal medicine residencies revealed that only 10% of programs offered any kind of modest curriculum in psychiatric education.[6] Regardless of this lack of preparation, hospitalists are called upon at each admission to make decisions that affect the psychiatric treatment of patients on psychotropic medication; namely, they must decide whether to continue or discontinue psychiatric medications. Many physicians reflexively discontinue a patient's chronic medications upon admission to the hospital; one study reported an adjusted odds ratio of between 1.18 and 1.86 for stopping a medication prescribed for a chronic condition.[7]

This review aims to assist the hospitalist in making an informed decision about the continuation of psychotropic medications in the medically ill patient. First, it examines the risks of stopping psychotropic medication, including psychiatric decompensation and discontinuation syndromes. It also explores the challenges of medication continuation in the context of changing pharmacokinetics and emerging side effects. Ultimately, physicians and patients must make collaborative decisions, weighing the risk of medication interactions against the potential adverse effects of psychiatric decompensation.

DISCONTINUATION

DRUG‐SPECIFIC DISCONTINUATION SYNDROMES

CONTINUATION

Reflexive discontinuation of psychotropic medications can clearly lead to adverse outcomes. However, when hospitalists decide to continue a patient's psychotropic medications, they must also be cognizant of potential complications. Modifications may be necessary because of hepatic, renal, or cardiac disease. In addition, physicians need to be aware of drug‐drug interactions. Pharmacotherapy for medically ill elderly patients may require dose modifications to account for an increased lipophilic volume of distribution and a decreased rate of metabolism.[33] Finally, pregnancy can present additional challenges regarding dose modifications and teratogenicity.

On the other hand, hospitalists must be aware that continuing a patient's psychotropic medication may not be the cause of new psychiatric symptoms. Drugs prescribed for medical disorders (eg, corticosteroids) often cause psychiatric symptoms. In addition, psychiatric symptoms may emerge at times of nonpsychotropic medication withdrawal or due to nonpsychotropic drug‐drug interactions.[4] Groups of medications commonly associated with psychiatric disturbances include analgesics, sedatives, anesthetics, anticonvulsants, and anticholinergics.

PHARMACOKINETICS: PSYCHOTROPIC TOXICITY

Medical illness alters the body's steady state, and renal or hepatic metabolism may be impaired when a patient requires hospitalization. Additionally, new medications may increase the effects of psychotropics, whether by intrinsic augmentation of effect or decreased psychotropic clearance. Ultimately, these changes can lead to psychotropic toxicity.

Specific toxicities merit discussion. First, serotonin syndrome is a potentially fatal condition. The majority of cases occur with synergistic serotonergic medication administration, though there are case reports of the syndrome occurring with addition of inhibitors of cytochrome p450 2D6 and/or 3A4 to SSRIs. A large number of medications from different classes have been indicated (Table 2).[34] Symptoms generally occur within 24 hours of medication administration and include mental status changes, autonomic instability, and neuromuscular hyperactivity. When serotonin syndrome is suspected, the offending agent should be discontinued immediately. There is no definitive treatment, though supportive care can be lifesaving.[34]

In addition to serotonin syndrome, hypertensive emergency may occur due to drug interactions with MAOIs. MAOIs inhibit the enzyme monoamine oxidase, resulting in elevated levels of serotonin, histamine, and catecholamines in the blood. Coadministration of MAOIs and sympathomimetic agents (such as cough suppressants and analgesics) may dangerously increase adrenergic stimulation, elevating blood pressure to the point of end‐organ damage. Please see Table 3 for a full list of drugs indicated in MAOI‐associated hypertensive crisis.[35] To ensure safety, it is recommended that MAOIs be discontinued for 14 days prior to introducing medications with sympathomimetic properties, and vice versa. Because of its longer half‐life, a 5‐week washout period is recommended for fluoxetine.[35]

Lithium toxicity may result from changing patient pharmacokinetics. Lithium is almost entirely renally excreted, and acute kidney injury may precipitously raise serum levels. Within the renal collecting system, lithium is handled similarly to sodium, with 80% reabsorbed from the proximal tubule to the collecting duct. Thus, factors that decrease glomerular filtration rate (GFR) and increase proximal tubule absorption will increase serum lithium levels. For example, decreased effective arterial volume (due to dehydration, cirrhosis, nephrotic syndrome, or heart failure) may elevate lithium levels. Additionally, medications that decrease GFR may increase lithium reabsorption. These include nonsteroidal anti‐inflammatory drugs, angiotensin‐converting enzyme inhibitors, and thiazide diuretics. Because of lithium's narrow therapeutic index, small elevations in serum levels can lead to toxicity. Severity of intoxication correlates with serum concentration. Symptoms range from lethargy, weakness, tremor, ataxia, and gastrointestinal distress to coma, seizures, renal failure, and death. Toxicity is also associated with electrocardiograph (ECG) changes, including ST‐segment depression and T‐wave inversion in the lateral precordial leads. Sinus node dysfunction can also occur. Definitive treatment for lithium toxicity is hemodialysis.[36]

Though the therapeutic index is much wider for valproic acid than for lithium, valproate toxicity may also occur in the medically ill patient with previously stable serum levels. Valproic acid is highly protein‐bound at therapeutic levels, and is metabolized largely through hepatic glucuronidation. Initiation of medications that compete for protein‐binding sites, including aspirin, has led to valproate toxicity. Moreover, acute liver failure or addition of drugs that compete with hepatic microsomal enzymes may lead to decreased excretion of valproic acid. Poisoning may result in central nervous system (CNS) and respiratory depression, hypotension, cerebral edema, and pancreatitis. True hepatoxicity is rare, though hyperammonemia is widely documented. Thrombocytopenia is the most common hematologic abnormality associated with overdose. However, thrombocytopenia may also occur without complication in patients on stable therapeutic doses. Treatment is largely supportive, though hemoperfusion and hemodialysis may be used when serum levels are >300 g/mL, as only 35% of the drug is protein‐bound at that level. Naloxone has been shown in case reports to reverse valproic acid‐induced coma, and L‐carnitine has been increasingly recommended for hyperammonemia.[37, 38]

PHARMACOKINETICS: DRUG‐DRUG INTERACTIONS

As discussed above, the addition of a new medication can increase previously stable levels of psychotropic drugs, leading to toxicity. Conversely, mental health medications can alter the expected metabolism of a drug being used to treat acute medical illness. Many psychotropics are metabolized via the cytochrome p450 enzyme, particularly the SSRIs (Table 4).[39] A number of antimicrobial and antiarrythmic medications are also cleared via this route, leading to potential toxic or subtherapeutic levels when drug‐drug interactions occur.

PSYCHOTROPIC ADVERSE EFFECTS

Psychotropic medications may also cause side effects that contribute to the clinical presentation, requiring ongoing monitoring, a dose reduction, or psychotropic discontinuation. Potential adverse effects that commonly impact psychopharmacologic management include anticholinergic side effects, cardiac effects, and sedation.

ANTICHOLINERGIC EFFECTS AND TOXICITY

Newly emerging anticholinergic effects may be particularly troubling. Dry mouth may cause swallowing difficulty and aspiration. Pupillary dilatation and dry eyes can increase risk of falls. Constipation may evolve into fecal impaction, and urinary retention can contribute to increased catheter use and infection. CNS effects are perhaps the most serious, ranging from drowsiness and memory impairment to frank delirium.[40]

Many psychotropic drugs are anti cholinergic. Among the antidepressants, the TCAs and paroxetine have the highest anticholinergic activity. Anticholinergic effects have also been reported with the low potency first generation neuroleptics and with the atypical antipsychotics olanzapine and clozapine. Additionally, medications used to treat the extrapyramidal symptoms associated with antipsychotics (such as benztropine and diphenhydramine) are strongly anticholinergic.[41] Patients without previous overt anticholinergic symptoms from these medications may experience adverse effects when hospitalized. Medical illness or new medications may alter psychotropic drug metabolism and elimination, leading to accumulation of their anticholinergic effects. Many medications used in the hospital also have intrinsic anticholinergic activity. These include some antiemetics, antispasmodics, antiarrhythmics, and histamine H2 receptor blockers. Elderly patients are particularly prone to anticholinergic effects due to age‐related deficits in cholinergic transmission.[40]

QTc PROLONGATION

QTc prolongation is a potentially lethal side effect of certain medications. Prolonged QTc increases the risk of cardiac mortality and sudden death, presumably related to onset of torsades de pointe. Certain antidepressants have consistently been associated with QTc prolongation, particularly the TCAs. In addition, the US Food and Drug Administration recently issued the recommendation that the SSRI citalopram not be used at doses >40 mg (and 20 mg in those with hepatic impairment or age >60 years) due to results of a randomized controlled trial that showed a dose‐response increase in QTc. Antipsychotic medications have also been shown to increase QTc, with the greatest evidence for thioridazine and the first‐generation, low‐potency neuroleptics. Haloperidol (particularly the intravenous formulation) has also been linked to both long QTc and torsades, though data may be confounded by the degree of medical illness of patients receiving the medication.[42] Of the atypicals, ziprasidone causes the greatest QTc prolongation.[43] However, a large retrospective cohort study showed similar risk increase of sudden cardiac death (2‐fold) among all antipsychotics (including typicals and atypicals) when examined individually.[44]

Additional risk factors for QTc prolongation abound in the hospitalized patient. These include many medical problems, including electrolyte abnormalities, heart conditions, renal and hepatic dysfunction, and CNS injury. Hospitalized patients are also exposed to the cumulative effects of medications that increase duration of QTc, such as class I and class III antiarrhythmics. Additionally, certain antimicrobials, including macrolide antibiotics and antifungals, have been associated with QTc prolongation via pharmacokinetic interactions.

Because of this, QTc should be measured upon admission in patients on stable doses of psychotropics that predispose to prolongation. Addition of other medications known to contribute to increased QTc should prompt further ECGs. Electrolytes, particularly potassium and magnesium, should be aggressively repleted. When QTc extends beyond 500 ms, consideration should be given to discontinuing or changing medications that can contribute to QTc prolongation (whether psychotropics or drugs used to treat acute medical problems).[42]

SEDATION

Sedation is another potential side effect of psychotropic medications. Although sedation is beneficial for agitation and anxiety, sedated patients may be unable to participate in treatment. They are also at greater risk of aspiration and falls.

Antipsychotics cause sedation through antagonism of 1 adrenergic and H1 histaminergic receptors. Effects are most pronounced with the low‐potency, first‐generation antipsychotics and the atypicals quetiapine and clozapine. Some antidepressants, including the TCAs and mirtazapine, also cause somnolence by histamine H1‐receptor antagonism. If a patient has been psychiatrically stable on a particular antipsychotic or antidepressant, but has psychotropic‐induced sedation that interferes with treatment, hospitalists may want to consider temporarily decreasing the dose.

Benzodiazepines induce sedation by increasing ‐aminobutyric acid‐ergic transmission. There is significant overlap between anxiolytic and sedating doses of benzodiazepines. The amount of sedation is related to dose, speed of absorption, and onset of CNS penetration. Thus, sedation may be minimized by using a lower dose or switching to an equivalent dose of a slower‐onset benzodiazepine.[45, 46]

CONCLUSION

The decision to continue or discontinue psychotropic medications is often challenging. It requires the hospitalist to carefully weigh the risks and benefits of the ongoing treatment versus discontinuation, while also considering the patient's preference whenever possible. Sudden cessation of psychotropics can lead to a number of unwanted complications, from mild withdrawal to life‐threatening autonomic instability and psychiatric decompensation. Yet psychotropic continuation can also lead to unwanted drug‐drug interactions and newly emergent side effects.

To improve patient safety and outcomes, hospitalists must take a cautious and well‐thought out approach to treating patients on psychotropic drugs. Reflexive cessation of home medications must be avoided. If hepatic or renal insufficiency develops, medication doses may need to be adjusted. When available, drug levels should guide dose adjustments. If side effects occur, the patient's medication list should be carefully reviewed for potential drug‐drug interactions. Maintaining mental health may mean substituting another drug for one that interferes with home psychotropic medications. Psychotropic doses may also be minimized to decrease side effects. When a psychotropic must be discontinued, tapering is recommended over an abrupt discontinuation, except in the case of an acute toxicity. Moreover, cross‐titration to another effective agent may prevent psychiatric decompensation.

Additionally, hospitalists should use all available resources when deciding on a patient's psychotropic regimen. Mobile devices and online resources can assist with pharmacokinetics. Pharmacists can help with more complex questions or potential drug substitutions. Consultation‐liaison psychiatrists can be a valuable resource in ensuring the safety and stability of a patient with psychiatric comorbidity within the medical environment. The consultant may assist by assessing a patient's current psychiatric state and recommending psychotropic medication changes when needed.