Implications of opioid-sparing medications in critically ill patients: A scoping review.

OBJECTIVE: The purpose of this scoping review was to evaluate literature involving opioid-sparing medications in critically ill patients with a focus on clinically meaningful outcomes. DESIGN: Scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. SETTING: Intensive care unit. PATIENTS OR PARTICIPANTS: Adult patients in an intensive care unit setting. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: PubMed and Cochrane Library were searched from October 1, 2019 to June 1, 2023. Inclusion criteria consisted of randomized controlled trials evaluating adjunctive analgesic use in adult patients in an intensive care unit setting. RESULTS: There were 343 citations and titles identified in the initial search, with 328 remaining after removal of duplicates, 294 excluded at title and abstract screening, 34 available for full text review, and six included in the scoping review. Most studies reported modest reductions in opioid use as a secondary endpoint. Improvement in clinical outcomes such as reduction in duration of mechanical ventilation or delirium were reported in two trials with dexmedetomidine. CONCLUSIONS: In recently published trials of adjunctive agents in critically ill patients, opioid-sparing effects were small. Data to support improvements in clinical outcomes remains limited.

Appraising the use of tranexamic acid in traumatic and non-traumatic intracranial hemorrhage: A narrative review.

Recently there has been increasing interest and debate on the use of tranexamic acid (TXA), an antifibrinolytic drug, in both traumatic and non-traumatic intracranial hemorrhage. In this review we aim to discuss recent investigations looking at TXA in traumatic brain injury (TBI) and different categories of spontaneous intracranial hemorrhage. We also discuss differences between setting (hospital vs pre-hospital), dosing and timing strategies, and other logistical challenges surrounding optimal use of TXA for isolated intracranial hemorrhage. Last, we hope to provide guidance for clinicians when considering the use of TXA in a patient with traumatic or non-traumatic intracranial hemorrhage based on appraisal of the available literature as well as some potential ideas for future research in this area.

Balanced Salt Solutions for Critically Ill Patients: Nonplused and Back to Basics.

OBJECTIVES: The purpose of this article is to summarize the results of major randomized controlled trials (RCTs) comparing clinical outcomes of critically ill patients treated with normal saline (NS) or balanced salt solutions (BSSs), address discordant results of these studies, and provide direction for future investigations. DATA SOURCES: PubMed (2011 to January 2022) with bibliographies of retrieved articles searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: RCTs comparing NS and BSSs in critically ill adult patients. DATA SYNTHESIS: Recently published large RCTs comparing NS with BSSs in heterogeneous populations of intensive care unit patients did not find significant differences in mortality, despite positive findings in some end points in prior RCTs. However, there were a number of methodologic issues common to the RCTs including: varying study designs and end points, clinician discretion for the majority or all treatments other than the primary intervention fluid, heterogeneous patients with varying levels of acuity, and lack of power to investigate potential subgroup differences. In addition, there were problematic issues related to blinding and use of nonstudy fluids. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Intravenous fluids are a mainstay of supportive care for critically ill patients. Similar to the so-called crystalloid-colloid debate, there has been a long-standing debate among critical care clinicians and researchers concerning the preferred crystalloid solution, NS versus one of the available BSSs. CONCLUSIONS: Despite the recent publication of large multicenter RCTs, the preferred resuscitation fluid, NS or a BSS, for critically ill patients is still open for debate, although the available investigations do provide some direction for clinicians and for future investigations.

Influence of Timing and Catecholamine Requirements on Vasopressin Responsiveness in Critically ill Patients with Septic Shock.

Introduction: Despite its widespread use, there is a paucity of data to guide the optimal use of arginine vasopressin (AVP) in critically ill patients with septic shock. Methods: This multicenter retrospective cohort study conducted in critically ill adults sought to evaluate the role of catecholamine requirements and timing on responsiveness to AVP. Responsiveness was defined as both a decrease in ≥ 50% of catecholamine requirements and no decrease in mean arterial pressure (MAP) at 4 hours post-AVP initiation. Primary outcomes of interest included the proportion of patients who started AVP within 4 hours after starting catecholamine therapy, as well as baseline norepinephrine (NE) equivalents (< 15, 15-39, or ≥ 40 mcg/min). Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness. Results: There were 300 patients included in this study, with 74 patients being responders and 226 being non-responders. There was no significant difference in the number of patients who received AVP within 4 hours from catecholamine initiation between responders and non-responders (35% vs. 42%, P = 0.29). There were more patients in the non-responder group requiring ≥ 40 mcg/min of NE equivalents at AVP initiation (30% vs. 16%, P = 0.023). Stress dose steroid use was less common in responders (35% vs. 52%, P = 0.011), which was consistent with logistic regression analysis (OR 0.56, 95% 0.32-0.98, P = 0.044). Clinical outcomes between responders and non-responders were similar, apart from ICU (5.4% vs. 19.5%) and hospital (5.4% vs. 20.4%) mortality being lower in responders (P = 0.0032 and P = 0.0002, respectively). Conclusion: Shorter times to AVP initiation was not associated with responsiveness at 4 hours post-catecholamine initiation, although non-responders tended to require higher doses of NE equivalents at time of AVP initiation. Concomitant corticosteroids were associated with a lower likelihood of AVP responsiveness.

Antibiotic prophylaxis for traumatic facial fractures.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this paper is to discuss the limitations of the evidence supporting the SIS recommendations for antibiotic prescribing in patients with traumatic facial fractures and to provide suggestions for clinical decision-making and further research in this area given the wide variation in prescribing practices. COMMENT: The Surgical Infection Society (SIS) recently published guidelines on antibiotic use in patients with traumatic facial fractures. The guidelines recommend against the use of prophylactic antibiotics for all adult patients with mandibular or non-mandibular facial fractures undergoing non-operative or operative procedures. Despite the available evidence, surveys conducted in the United States and the United Kingdom prior to the publication of the SIS guidelines demonstrate substantial preoperative, intraoperative and postoperative prophylactic prescribing of antibiotics for patients with facial fractures undergoing surgery. WHAT IS NEW AND CONCLUSION: With the exception of strong recommendations based on moderate-quality evidence to avoid prolonged postoperative antibiotic prophylaxis, the weak recommendations in the guidelines are a function of low-quality evidence. A logical choice for a narrow-spectrum antibiotic is cefazolin administered within 1 h of surgery and no longer than 24 h after surgery, since it is the gold standard of comparison based on clinical practice guidelines concerning antibiotic prophylaxis.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Utilization and Associated Costs in General Ward Patients.

BACKGROUND: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. OBJECTIVE: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin use in general ward patients. METHODS: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist-led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. RESULTS: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. CONCLUSION AND RELEVANCE: Clinical pharmacist-led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist-led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Heparin dosing for venous thromboembolism prophylaxis in obese hospitalized patients: An observational study.

OBJECTIVE: To compare rates of VTE occurrence in obese versus non-obese hospitalized patients who received UFH 5000 units subcutaneously q8 h. MATERIALS AND METHODS: This was a retrospective cohort study conducted in an academic medical center in the United States. Consecutive adult patients who were hospitalized during a 1-year time frame (2015) receiving UFH 5000 units subcutaneously q8 h for VTE prophylaxis. The primary outcome was occurrence of VTE during hospitalization. This was compared between obese (body mass index ≥30 kg/m2) and non-obese (body mass index <30 kg/m2) patients. Secondary outcomes included the occurrence of significant bleeding (i.e. intracranial and gastrointestinal hemorrhage). RESULTS: There were 5110 patients included in the study cohort, with a mean age of 57 ±â€¯18 years; and 54% (n = 2757) were male. A similar proportion of patients in the obese group (n = 11/1673, 0.7%) and non-obese group (n = 19/3437, 0.6%) developed a VTE (difference 0.1%, 95% CI -0.4 to 0.6%, p = 0.70). The incidence of VTE was also low (n = 1/394, 0.3%) in patients with body mass index ≥40 kg/m2. Intracranial bleeding occurred in 3 (0.2%) patients in the obese group and 2 (0.1%) patients in the non-obese group (difference 0.1%, 95% CI -0.1 to 0.3%, p = 0.34). Gastrointestinal bleeding occurred in 6 (0.4%) patients in the obese group and 13 (0.4%) patients in the non-obese group (difference 0%, 95% CI -0.4 to 0.3%, p > 0.99). CONCLUSIONS: UFH 5000 units subcutaneously q8 h may be sufficient for prevention of VTE in obese patients.

Effect of Amantadine on Agitation in Critically Ill Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to compare the presence of agitation in traumatic brain injury patients treated with amantadine with those not treated with amantadine in the intensive care unit (ICU). METHODS: This was a retrospective cohort study conduced in a trauma ICU of a tertiary care institution in the United States. Patients who received amantadine were compared with patients who did not receive amantadine. The primary outcome measure was the presence of agitation, defined as the Richmond Agitation Sedation Scale score of +2 or higher. Secondary comparisons included haloperidol use, benzodiazepine use, opioid use, and ICU length of stay. RESULTS: A total of 139 patients were included in the study cohort (70 patients in the amantadine group, 69 patients in the no-amantadine group). There were more patients who had agitation in the amantadine group (38% vs 14%, P = 0.018). Patients who received amantadine received more opioids in fentanyl equivalents (10.3 [interquartile range {IQR}, 6.3-20.4] µg/kg vs 7.4 [IQR, 2.1-12.6] µg/kg, P = 0.009) and had a longer ICU length of stay (4.5 [IQR, 3-10] days vs 3 [IQR, 2-5] days, P = 0.010). Haloperidol use and benzodiazepine use were similar between groups. CONCLUSIONS: The early use of amantadine after traumatic brain injury may increase the risk of agitation. This could increase opioid consumption and ICU length of stay.

Methocarbamol use is associated with decreased hospital length of stay in trauma patients with closed rib fractures.

BACKGROUND: The objective of this study was to evaluate the effect of methocarbamol on hospital length of stay in patients with closed rib fracture injuries. METHODS: This was a retrospective cohort study conducted in an academic medical center in the United States. Adult trauma patients, who sustained closed rib fractures, were included. Patients were categorized based on whether they received methocarbamol or not during admission. The primary outcome of interest was time to hospital discharge in days (i.e. length of hospital stay). A Cox Proportional Hazards Model was constructed to determine if methocarbamol use was associated with a greater likelihood of earlier discharge. RESULTS: A total of 592 patients were included in the final study cohort. Of these, 329 received methocarbamol and 263 did not receive methocarbamol. In the Cox Proportional Hazards Model methocarbamol use was associated with a greater likelihood of being discharged from the hospital (HR 1.47, 95% CI 1.21 to 1.78, p < 0.001). . CONCLUSIONS: The use of methocarbamol after traumatic rib fractures may result in a reduction in the length of hospital stay.

Effect of Methocarbamol on Acute Pain After Traumatic Injury.

There is interest in the use of methocarbamol as an adjunctive agent for pain control after traumatic injury. The primary objective of this study was to determine the effect of methocarbamol on pain measurements after acute injury. This was a retrospective, matched cohort study conducted at an academic medical center in the United States. Consecutive adult (age ≥18 years) patients who were admitted to the hospital between June 1, 2012 and June 30, 2013 because of a traumatic injury were evaluated. Patient cases receiving methocarbamol for at least 3 days were matched to controls that did not receive methocarbamol based on age, sex, and injury severity. The primary outcome measures of pain scores were assessed on numerical rating scale from 0 to 10 (0 = no pain; 10 = worst possible pain) and conducted during routine patient care. A total of 200 patients were included in the final cohort (100 in each group). In the overall cohort, the mean age was 49 ± 22 years, 67% were men, and mean International Classification of Disease-derived Injury Severity Score was 0.8 ± 0.1 in both groups. There was no significant association between methocarbamol use and mean pain score on day 1 [coefficient 0.09, 95% confidence interval (CI), -0.57 to 0.75, P = 0.782, model R = 0.43], day 2 (coefficient 0.47, 95% CI, -0.15 to 1.09, P = 0.140, model R = 0.42), or day 3 (coefficient 0.51, 95% CI, -0.13 to 1.16, P = 0.117, model R = 0.42) after injury. Methocarbamol did not improve pain control after traumatic injury during the first 3 days of hospitalization.

Cost savings with interventions to reduce aerosolized bronchodilator use in mechanically ventilated patients.

PURPOSE: The purpose of this evaluation is to describe the cost savings associated with multimodal interventions aimed at reducing aerosolized bronchodilator use in mechanically ventilated patients without adversely affecting costs associated with length of stay (LOS). MATERIALS AND METHODS: Subjects were included in the analysis if they were aged more than 18 years, on mechanical ventilation in the intensive care unit, and received aerosolized bronchodilators. Patients were excluded if they had reversible airway disease, an indication needing bronchodilator therapy. Patient data were obtained using the University Health System Consortium Clinical Data Base/Resource Manager (Chicago, IL) to compare outcomes during two 6-month periods separated by a 4-month intervention phase aimed to reduce bronchodilator use. RESULTS: There were no significant differences in age, sex, and LOS (observed and expected) between the preintervention and postintervention phases. Based on whole acquisition costs, the total cost of bronchodilators dispensed to the adult intensive care units over the 6-month postintervention phase was reduced by $56960 compared with the 6-month preintervention phase ($120562 vs $63602, respectively). CONCLUSIONS: Multimodal efforts to restrict aerosolized bronchodilator therapy in mechanically ventilated patients were successful and led to sustained reductions in use that was associated with substantial reductions in cost, without affecting LOS.

Vancomycin dosing for pneumonia in critically ill trauma patients.

BACKGROUND: Vancomycin has been recommended as the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia with a desired trough concentration of 15 to 20 mg/L. The purpose of this study was to evaluate the initial dosing of vancomycin for MRSA pneumonia in critically ill adult trauma patients. METHODS: Critically ill adult trauma patients were retrospectively identified for inclusion into the study. Patients initiated at a dose of 1 g intravenously (i.v.) every 8 hours were compared with patients initiated at a dose of 1 g i.v. every 12 hours. Baseline continuous demographic variables and steady-state vancomycin trough concentrations were compared between the two groups using a Student's t test (alpha = 0.05). RESULTS: There were 36 patients who satisfied criteria for inclusion, 17 patients in the 1 g every 8 hour group and 19 patients in the 1 g every 12 hour group. The mean steady-state trough concentration was higher in the 1 g every 8 hour group versus the 1 g every 12 hour group (11.1 vs. 6.8 mg/L, p = 0.014). A steady-state trough concentration greater than 15 mg/L was achieved in 23.5% of the patients in the 1 g every 8 hour group and none of the patients in the 1 g every 12 hour group. CONCLUSION: A vancomycin regimen of 1 g i.v. every 12 hours in critically ill trauma patients with MRSA pneumonia and normal renal function is unlikely to achieve trough concentrations of 15 to 20 mg/L. Doses of at least 1 g i.v. every 8 hours are needed.

Cost implications of and potential adverse events prevented by interventions of a critical care pharmacist.

PURPOSE: The cost implications of and potential adverse events prevented by the interventions of a critical care pharmacist were studied. METHODS: A decentralized clinical pharmacist assigned to a surgical intensive care unit (ICU) documented all interventions made from mid-October 2003 through February 2004 using a standardized written form. The data were retrospectively evaluated and the following information was extracted: amount of time spent performing various clinical activities, how drug-related problems were identified (e.g., order entry versus chart review), and a general description of the interventions. The interventions were independently reviewed by two other clinical pharmacists to determine whether an actual or potential adverse drug event (ADE) would have occurred without the intervention, the probability that an ADE would have occurred without the intervention, the type of intervention, and potential cost avoidance of the intervention. Once the evaluations were completed, the data obtained from order entry and verification activities were compared with the data obtained during other clinical functions. RESULTS: A total of 129 interventions were documented over 4.5 months. The majority of interventions were identified during chart review (40%) and patient care rounds (39%). The potential cost avoidance of the documented interventions was $205,919-$280,421. Interventions identified during patient care rounds and chart review were most likely to achieve the greatest impact on cost avoidance. CONCLUSION: Among the interventions performed and documented by a clinical pharmacist in an ICU, patient care rounds and chart-review activities were associated with the greatest number of interventions and the greatest potential cost avoidance.

Direct observation approach for detecting medication errors and adverse drug events in a pediatric intensive care unit.

OBJECTIVE: To determine the incidence, type, and stage of occurrence of medication errors and potential and actual adverse drug events (ADEs) in a pediatric intensive care unit (ICU) using trained observers. The preventability and severity of ADEs and the system failures leading to medication error occurrence were also investigated. DESIGN: Prospective, direct observation study. SETTING: A 16-bed pediatric medical/surgical ICU at a tertiary care academic medical center. PATIENTS: One enrolled nurse caring for at least one pediatric ICU patient age <18 yrs was randomly chosen during each observation period. INTERVENTIONS: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. MEASUREMENTS AND MAIN RESULTS: Medication errors and potential and actual ADEs were identified throughout the entire medication use process. The 26 12-hr observation periods included 357 reviewed written orders and 263 observed doses. The study observers identified 58 incidents, which were subsequently classified by the evaluators according to clinical importance, severity, and preventability. Fifty-two of these incidents were considered medication errors; six incidents were determined to be nonpreventable ADEs. Of the 52 medication errors, 42 (81%) were considered clinically important. Potential ADEs comprised 35 (83%) of these important medication errors; the other seven (17%) were classified as actual, preventable ADEs. Overall, the actual and potential ADE rate occurred at 3.6 events and 9.8 events per 100 orders, respectively. CONCLUSIONS: Our medication error rate was similar to that of previous pediatric ICU studies that used the direct observation method for reporting but higher than the rates in previous studies using other detection techniques such as voluntary incident reporting. Periodic direct observation and other ongoing data collection methods such as voluntary incident reporting have the potential to be complementary approaches to medication error and ADE detection.

Medication errors and adverse drug events in an intensive care unit: direct observation approach for detection.

OBJECTIVE: To determine the incidence and preventability of medication errors and potential/actual adverse drug events. To evaluate system failures leading to error occurrence. DESIGN: Prospective, direct observation study. SETTING: Tertiary care academic medical center. PATIENTS: Patients in a medical/surgical intensive care unit. INTERVENTIONS: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. MEASUREMENTS AND MAIN RESULTS: The observers identified 185 incidents during a pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two independent evaluators concluded that 13 of 35 (37%) actual adverse drug events were nonpreventable (i.e., not medication errors). An additional 40 of the remaining 172 medication errors were judged not to be clinically important. Of the 132 medication errors classified as clinically important, 110 (83%) led to potential adverse drug events and 22 (17%) led to actual, preventable adverse drug events. There was one error (i.e., resulting in a potential or actual, preventable adverse drug event) for every five doses of medication administered. The potential adverse drug events mostly occurred in the administration and dispensing stages of the medication use process (34% in each); all of the actual, preventable adverse drug events occurred in the prescribing (77%) and administration (23%) stages. Errors of omission accounted for the majority of potential and actual, preventable adverse drug events (23%), followed by errors due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%), and drug-drug interaction (10%). CONCLUSIONS: Using a direct observation approach, we found a higher incidence of potential and actual, preventable adverse drug events and an increased ratio of potential to actual, preventable adverse drug events compared with studies that used chart reviews and solicited incident reporting. All of the potential adverse drug events and approximately two thirds of the actual adverse drug events were judged to be preventable. There was one preventable error for every five doses of medication administered; most errors were due to dose omission, wrong dose, wrong drug, wrong technique, or interactions.