Citations

The objective of this study is to describe the pharmacokinetics of lacosamide in a critically ill adult during continuous venovenous hemofiltration (CVVH). A 78-year-old male developed sepsis and acute kidney injury following cardiac surgery. He was initially treated with intermittent hemodialysis but developed nonconvulsive status epilepticus at the end of the first session and was subsequently initiated on CVVH. In addition to lorazepam boluses, levetiracetam, and midazolam infusion, he was loaded with lacosamide 400 mg intravenously and started on 200 mg intravenously twice daily as maintenance therapy. Noncompartmental modeling of lacosamide pharmacokinetics revealed significant extracorporeal removal, a volume of distribution of 0.69 L/kg, elimination half-life of 13.6 hours, and peak and trough concentrations of 7.4 and 3.7 mg/L, respectively (goal trough, 5-10 mg/L). We found significant extracorporeal removal of serum lacosamide during CVVH, which was higher than previously reported. This led to subtherapeutic concentrations and decreased overall antiepileptic drug exposure. The relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations.

Study ObjectiveHigh‐dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point‐of‐care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results.DesignProspective observational pilot study.SettingIntensive care unit in a large academic tertiary care medical center.PatientsFive consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy.Measurements and Main ResultsThe performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland‐Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland‐Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action.ConclusionThe accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.

AbstractBackgroundNephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal β-lactam/VAN combinations.MethodsThe study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal β-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.ResultsThe overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).ConclusionShort courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.

This article aims to describe a rare cause of severe encephalitis in 2 cases of infants with signs of intracranial hypertension and severe autonomic dysregulation. The authors conclude that human parechoviruses are becoming a more recognized cause of encephalitis because of the increasing use of rapid detection methods. With early recognition of this clinical entity, improved care can be administered.

BACKGROUND: Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. RESULTS: A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9–9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

Objectives: Our primary aim was to determine the factors leading to prophylactic endotracheal intubation in intensive care unit (ICU) patients undergoing gastrointestinal endoscopy. Secondary aims were to determine the rate of unplanned endotracheal intubations during endoscopy and to determine the rate of aspiration following endoscopy for patients admitted to the ICU. Methods: Critically ill adult (≥18 years) patients who underwent upper and lower endoscopic procedures from January 2012 to July 2016 in a medical/surgical ICU were included. Determinants of prophylactic endotracheal intubation prior to endoscopy as well as other postprocedure outcomes were electronically captured by a validated data mart system. Given our focus on aspiration in those who were not endotracheally intubated prior to endoscopy, we used a validated definition a priori. Results: A total of 320 patients were included in the final analysis: 76(24%) were intubated prior to endoscopy and 244 (76%) were not. The endotracheally intubated group had a significantly higher Acute Physiologic and Chronic Health Evaluation III (44.5 [16.2] vs 39.5 [15.5]; P = .02) and Sequential Organ Failure Assessment (6.9 [4.4] vs 3.8 [3]; P ≤ .01) scores, higher rate of hematemesis within 24 hours of endoscopy (28 [37%] vs 45 [18%]; P ≤ .01), and higher rate of upper endoscopy (72 [96%] vs 181 [74%]; P ≤ .01). We composed a composite outcome for multivariable analyses, which demonstrated the rate of any complication was significantly higher among those who were intubated prior to the procedure versus those who were not intubated previously (odds ratio: 2.80, 95% confidence interval (CI): 1.16-6.72, P = .02). Conclusion: Endoscopy performed in the ICU without endotracheal intubation is safe. However, patient selection for prophylactic intubation prior to endoscopy is of critical importance as illustrated in this study with higher illness severity, planned upper endoscopy, and hematemesis 24 hours prior being key factors on deciding to perform endotracheal intubation. Prophylactic intubation for endoscopy and preexisting cardiac disease were associated with a higher rate of adverse outcomes.

Objectives: Our primary aim was to ascertain the frequency of postintubation hypotension in immunocompromised critically ill adults with secondary aims of arriving at potential risk factors for the development of postintubation hypotension and its impact on patient-related outcomes. Methods: Critically ill adult patients (≥18 years) were included from January 1, 2010, to December 31, 2014. We defined immunocompromised as patients with any solid organ or nonsolid organ malignancy or transplant, whether solid organ or not, requiring current chemotherapy. Postintubation hypotension was defined as a decrease in systolic blood pressure to less than 90 mm Hg or a decrease in mean arterial pressure to less than 65 mm Hg or the initiation of any vasopressor medication. Patients were then stratified based on development of postintubation hypotension. Potential risk factors and intensive care unit (ICU) outcome metrics were electronically captured by a validated data mart system. Results: The final cohort included 269 patients. Postintubation hypotension occurred in 141 (52%; 95% confidence interval: 46-58) patients. Several risk factors predicted postintubation hypotension on univariate analysis; however, only Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability remained significant on all 4 multivariate analyses. Patients developing postintubation hypotension had higher ICU and hospital mortality (54 [38%] vs 31 [24%], P = .01; 69 [49%] vs 47 [37%], P = .04). Conclusion: Based on previous literature, we found a higher frequency of postintubation hypotension in the immunocompromised than in the nonimmunocompromised critically ill adult patients. Acute Physiology and Chronic Health Evaluation III score in the first 24 hours, preintubation shock status, and preintubation hemodynamic instability were significant predictors on multivariate analyses. Postintubation hypotension led to higher ICU and hospital mortality in those experiencing this complication.

BACKGROUND: Critically ill patients frequently receive plasma transfusion under the assumptions that abnormal coagulation test results confer increased risk of bleeding and that plasma transfusion will decrease this risk. However, the effect of prophylactic plasma transfusion remains poorly understood. The objective of this study was to determine the relationship between prophylactic plasma transfusion and bleeding complications in critically ill patients. METHODS: This is a retrospective cohort study of adults admitted to the intensive care unit (ICU) at a single academic institution between January 1, 2009 and December 31, 2013. Inclusion criteria included age ≥18 years and an international normalized ratio measured during ICU admission. Multivariable propensity-matched analyses were used to evaluate associations between prophylactic plasma transfusion and outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of hospital- and ICU-free days and mortality within 30 days of ICU discharge. RESULTS: A total of 27,561 patients were included in the investigation with 2472 (9.0%) receiving plasma therapy and 1105 (44.7%) for which plasma transfusion was prophylactic in nature. In multivariable propensity-matched analyses, patients receiving plasma had higher rates of red blood cell transfusion (odds ratio: 4.3 [95% confidence interval: 3.3–5.7], P < .001) and fewer hospital-free days (estimated % increase: −11.0% [95% confidence interval: −11.4, −10.6%], P < .001). There were no significant differences in ICU-free days or mortality. These findings appeared robust, persisting in multiple predefined sensitivity analyses. CONCLUSIONS: Prophylactic administration of plasma in the critically ill was not associated with improved clinical outcomes. Further investigation examining the utility of plasma transfusion in this population is warranted.