Evaluation of phenobarbital for prevention of alcohol withdrawal in trauma patients.

BACKGROUND: Up to 30% of trauma patients experience alcohol withdrawal syndrome (AWS) during their hospital admission, which is associated with worse outcomes. While benzodiazepines and phenobarbital are the mainstay of AWS management, there are limited data on the prevention of AWS. The objective was to evaluate the safety and efficacy of phenobarbital for the prevention of AWS. METHODS: Adult patients admitted to a level 1 trauma center who received at least one dose of phenobarbital for the prevention of AWS between January 2019 and August 2021 were included. Patients were case matched to a control group managed with symptom-triggered therapy based on risk of AWS. Risk factors included sex, age, history of AWS/delirium tremens or withdrawal seizures, selected laboratory values, and screening questionnaires. The primary endpoint was the need for rescue therapy. Secondary endpoints included the time to rescue therapy, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: Overall, 110 patients were included with 55 patients in each group. The phenobarbital group had higher baseline Injury Severity Scores ( p = 0.03) and were more likely to be admitted to the ICU (44% vs. 24%; p = 0.03). The phenobarbital group required less rescue therapy (16% vs. 62%; p < 0.001) with a longer time to rescue therapy administration (26 vs. 11 hours; p = 0.01). The phenobarbital group had a longer hospital LOS (216 vs. 87 hours; p = 0.0001) but no difference in ICU LOS ( p = 0.36). There was no incidence of delirium tremens or seizures and no difference in intubation rates ( p = 0.68). There was no incidence of hypotension associated with phenobarbital. CONCLUSION: Patients managed with phenobarbital had a lower need for rescue therapy for AWS with no increased adverse effects. Further studies should evaluate a protocol to prevent alcohol withdrawal in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Evaluation of glucose management during therapeutic hypothermia at a Tertiary Academic Medical Center.

STUDY AIM: Alterations in metabolic function during therapeutic hypothermia (TH) decrease responsiveness to insulin and increase the risk of hyperglycemia. Glycemic control is associated with improved outcomes in selected patients; however, glycemic management strategies during TH are not defined. The objective of this analysis was to evaluate the glycemic metrics and IV insulin administration in critically ill patients during the cooling and rewarming phases of TH. METHODS: Data from 37 patients who received at least 6h of therapeutic hypothermia for cardiac arrest between January 2007 and January 2010 were retrospectively evaluated, 14 (37.8%) of whom had diabetes. RESULTS: The mean blood glucose was 9.16±3.22mmol/L and 6.54±2.45mmol/L; p<0.01 during cooling and rewarming, respectively. Twelve (32.4%) patients experienced at least one hypoglycemic event, defined as a blood glucose <4mmol/L. Nineteen (51.4%) patients experienced at least one hyperglycemic event, defined as a blood glucose >11.11mmol/L and 15 (40.5%) patients received IV insulin therapy. Patients on IV insulin had a higher incidence of diabetes (9 vs. 5; p<0.05), higher admission blood glucose (13.89±6.13 vs. 11.03±4.65mmol/L; p=0.11), and a higher incidence of hyperglycemia (14 vs. 2; p<0.01) and hypoglycemia (8 vs. 4; p<0.05). Of the patients on IV insulin, mean insulin requirements during cooling and rewarming were 15.2±16.1 and 7±12.5units/h, respectively. CONCLUSION: TH is commonly associated with hyperglycemia, hypoglycemia, and the use of IV insulin therapy. Further research is needed to determine optimal glycemic management strategies to prevent hyper- and hypoglycemia in patients during the different phases of TH.

Evaluation of an institution-wide guideline for hyperglycemic emergencies at a tertiary academic medical center.

BACKGROUND: No previous studies exist examining implementation of an institution-wide guideline and order set for hyperglycemic emergencies (diabetic ketoacidosis [DKA] and hyperosmolar hyperglycemic state [HHS]). OBJECTIVE: Evaluate the impact of an institutional guideline and order set for hyperglycemic emergencies. METHODS: This retrospective descriptive study evaluated patients with a diagnosis of DKA or HHS. Two time periods were evaluated: phase 1 (PRE) assessed practice preguideline implementation, and phase 2 (POST) assessed practice postguideline and order set introduction. RESULTS: A total of 172 patients (91 PRE and 81 POST) were included in the analysis. There was no difference in the mean hospital length of stay (LOS) in the PRE versus POST groups (5.2 ± 4 vs 5.9 ± 8.6 days, P = .49). The mean intensive care unit (ICU) LOS was shorter in the POST group (64.8 ± 19 vs 37.1 ± 74.8 hours, P < .01). The POST group had an increase in frequency of assessments for clearance of urinary ketones (18 vs 33.3%, P = .03) and ß-hydroxybutyrate (16 vs 37%, P < .01). Frequency of point-of-care glucose testing (12.5 ± 4.6 vs 15.1 ± 4.7, P < .01) and time to anion gap closure (13 ± 9 vs 9.3 ± 7.4 hours, P < .01) improved in the POST group. There was no difference in the number of patients experiencing hypoglycemia or hypokalemia between both groups. CONCLUSIONS: Implementation of an institutional guideline and order set for hyperglycemic emergencies decreased ICU LOS and time to anion gap closure, with no difference in rates of hypoglycemia.

Use of antiepileptics for seizure prophylaxis after traumatic brain injury.

PURPOSE: Antiepileptics used for seizure prophylaxis after traumatic brain injury (TBI) are reviewed. SUMMARY: Of the 275,000 people who are hospitalized with TBI each year, approximately 5-7% experience a posttraumatic seizure (PTS). According to the latest guidelines issued by the Brain Trauma Foundation and the American Academy of Neurology (AAN) for the management of severe TBI, PTS prophylaxis is recommended only during the first seven days after TBI. Of the available antiepileptic drugs, phenytoin has been the most extensively studied for the prophylaxis of PTS. Phenobarbital, valproate, and carbamazepine have not been as extensively researched, and, given their adverse-effect profiles and pharmacodynamic properties, there is no advantage to using these agents over phenytoin. Levetiracetam has demonstrated comparable efficacy to phenytoin for PTS prophylaxis and is associated with fewer adverse effects and monitoring considerations; it may be a reasonable alternative to phenytoin. However, levetiracetam has been associated with an increased seizure tendency. The Brain Trauma Foundation recommends using phenytoin for early PTS prophylaxis. The guidelines also state that valproate has demonstrated similar efficacy to phenytoin but warn that its use may be associated with increased mortality. CONCLUSION: The available literature supports the use of antiepileptics for early PTS prophylaxis during the first week after a TBI. Phenytoin has been extensively studied for this indication and is recommended by the AAN and Brain Trauma Foundation guidelines for early PTS prophylaxis. Levetiracetam has demonstrated comparable efficacy to phenytoin for early PTS prophylaxis and may be a reasonable alternative to consider in this patient population.

Introduction to drug pharmacokinetics in the critically ill patient.

Despite regular use of drugs for critically ill patients, overall data are limited regarding the impact of critical illness on pharmacokinetics (PK). Designing safe and effective drug regimens for patients with critical illness requires an understanding of PK. This article reviews general principles of PK, including absorption, distribution, metabolism, and elimination, and how critical illness can influence these parameters. In the area of drug absorption, we discuss the impact of vasopressor use, delayed gastric emptying and feeding tubes, and nutrient interactions. On the topic of drug distribution, we review fluid resuscitation, alterations in plasma protein binding, and tissue perfusion. With drug metabolism, we discuss hepatic enzyme activity, protein binding, and hepatic blood flow. Finally, we review drug elimination in the critically ill patient and discuss the impact of augmented renal clearance and acute kidney injury on drug therapies. In each section, we highlight select literature reviewing the PK impact of these conditions on a drug PK profile and, where appropriate, provide general suggestions for clinicians on how to modify drug regimens to manage PK challenges.

Technology utilization to prevent medication errors.

Medication errors have been increasingly recognized as a major cause of iatrogenic illness and system-wide improvements have been the focus of prevention efforts. Critically ill patients are particularly vulnerable to injury resulting from medication errors because of the severity of illness, need for high risk medications with a narrow therapeutic index and frequent use of intravenous infusions. Health information technology has been identified as method to reduce medication errors as well as improve the efficiency and quality of care; however, few studies regarding the impact of health information technology have focused on patients in the intensive care unit. Computerized physician order entry and clinical decision support systems can play a crucial role in decreasing errors in the ordering stage of the medication use process through improving the completeness and legibility of orders, alerting physicians to medication allergies and drug interactions and providing a means for standardization of practice. Electronic surveillance, reminders and alerts identify patients susceptible to an adverse event, communicate critical changes in a patient's condition, and facilitate timely and appropriate treatment. Bar code technology, intravenous infusion safety systems, and electronic medication administration records can target prevention of errors in medication dispensing and administration where other technologies would not be able to intercept a preventable adverse event. Systems integration and compliance are vital components in the implementation of health information technology and achievement of a safe medication use process.

Evaluation of the impact of a tele-ICU pharmacist on the management of sedation in critically ill mechanically ventilated patients.

BACKGROUND: An organized and uniform approach to managing sedation in critically ill patients has been associated with improved outcomes, but the most effective means of optimizing sedative medication use in clinical practice has not been fully determined. Pharmacist interventions directed at improving sedation guideline compliance have been shown to reduce the duration of mechanical ventilation. OBJECTIVE: To determine the impact that pharmacy staffing configurations that include a tele-ICU pharmacist have on compliance with an intensive care unit (ICU) sedation guideline in critically ill mechanically ventilated patients requiring continuous-infusion sedative medications. METHODS: Compliance with an established ICU sedation guideline, the performance of daily sedative interruptions, and the number of sedative medication-related interventions were evaluated before and after expansion of the ICU pharmacist staffing model to include comprehensive off-hours pharmacist coverage supported with established tele-ICU resources. In both groups, sedation was managed by the primary ICU team. In the intervention group, a pharmacist working in the tele-ICU center performed electronic record audits and made sedative medication recommendations to the primary team. RESULTS: The addition of third shift tele-ICU pharmacist support was associated with a significant increase in the percentage of patients who received a daily sedative interruption (45% vs 54%; p < 0.0001). This occurred in the context of significant increases in the total number of ICU pharmacist interventions (36 vs 49.4 per 100 patient days, p < 0.0001), the number of therapeutic interventions (20.4 vs 26.1 per 100 patient days, p < 0.001), and the number of sedative-related interventions (0.9 vs 4.4 per 100 patient days, p < 0.0001). CONCLUSIONS: Tele-ICU resources can be utilized to increase compliance with an established ICU sedation guideline and extend the benefits that daytime ICU clinical pharmacy services provide. Increased ICU pharmacist availability may have additional benefits not measured in this study.

Propylene glycol-induced lactic acidosis in a patient receiving continuous infusion pentobarbital.

OBJECTIVE: To report a case of probable propylene glycol (PG) toxicity in a patient receiving continuous infusion of pentobarbital for refractory status epilepticus. CASE SUMMARY: A 59-year-old woman with a declining mental status was admitted to the intensive care unit for management of status epilepticus. After failing to achieve the therapeutic endpoint of electroencephalogram burst suppression with a continuous infusion of propofol, the sedative regimen was changed to continuous infusion of pentobarbital. The patient received a loading dose of 450 mg (5 mg/kg), and the maintenance infusion was titrated to a dose of 10 mg/kg/h to achieve burst suppression. Twelve hours after the pentobarbital infusion was started, the patient developed an anion gap metabolic acidosis, elevated serum lactate level, hyperosmolality, and increased osmolal gap. The pentobarbital infusion was discontinued, and the patient's acidosis and hyperosmolality resolved. DISCUSSION: Pentobarbital contains 40% v/v of PG, which was thought to be a potential source of the patient's metabolic derangements. Reports of toxicity with drugs containing PG, particularly intravenous lorazepam, have been well described in the literature. What we describe, however, is one of few reports involving intravenous pentobarbital. The Naranjo probability scale supports a probable drug-related adverse event in our patient. CONCLUSIONS: PG toxicity is a potential complication associated with intravenous pentobarbital. Practitioners should be aware of the PG content of pentobarbital and should be familiar with the signs and symptoms associated with PG toxicity.