Analgosedation in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation Support.

Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized intervention for cardiopulmonary failure. Analgosedation during ECMO support is essential to ensure adequate pain and agitation control and ventilator synchrony, optimize ECMO support, facilitate patient assessment, and minimize adverse events. Although the principles of analgosedation are likely similar for all critically ill patients, ECMO circuitry alters medication pharmacodynamics and pharmacokinetics. The lack of clinical guidelines for analgosedation during ECMO, especially at times of medication shortage, can affect patient management. Here, we review pharmacological considerations, protocols, and special considerations for analgosedation in critically ill adults receiving ECMO support.

Levocarnitine supplementation for management of hypertriglyceridemia in patients receiving parenteral nutrition.

BACKGROUND: Levocarnitine deficiency has been observed in patients receiving parenteral nutrition (PN) and can cause or worsen hypertriglyceridemia. The objective was to characterize use of levocarnitine supplementation in PN and evaluate its effect on triglyceride levels in hospitalized adults. METHODS: This retrospective, single-center study included patients with triglyceride levels ≥175 mg/dl while receiving PN who had a subsequent reduction in lipid injectable emulsion dose. A piecewise linear regression was used to evaluate trends in triglyceride levels before and after the intervention, defined as initiation of levocarnitine in PN for the levocarnitine group, or reduction in lipid injectable emulsion alone for the control group. RESULTS: Two hundred sixty-one patients who received PN had an elevated triglyceride level and lipid injectable emulsion dose reduction, of which 97 (37.2%) received levocarnitine in PN. The median (IQR) levocarnitine dose added to PN was 8.0 (5.7-9.9) mg/kg. Triglyceride levels at 30 days post-intervention did not differ between groups (125 vs 176 mg/dl, P = .345). The addition of levocarnitine to PN was associated with a significantly greater rate of reduction in triglyceride levels pre-intervention to post-intervention compared with a reduction in lipid injectable emulsion alone (-11 vs -3 mg/dl per day; 95% CI, -15 to -2; P = .012). CONCLUSION: In hospitalized adults with hypertriglyceridemia who had a lipid injectable emulsion dose reduction, the addition of levocarnitine in PN was not associated with a difference in triglyceride levels at 30 days; however, a greater rate of improvement in pre-intervention to post-intervention triglyceride levels was observed.

Comparison of Clinical Scoring Tools to Predict Heparin-Induced Thrombocytopenia in Cardiac Surgery.

The 4Ts and HIT-Expert Probability (HEP) scoring tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients, and the reported sensitivity and specificity of the Post-Cardiopulmonary Bypass (CPB) scoring tool vary widely in the 2 available analyses. It remains unclear which of the available scoring tools most accurately predicts HIT in this population. Forty-nine HIT-positive patients who underwent on-pump cardiac surgery within a 6-year period were loosely matched to 98 HIT-negative patients in a 1:2 case-control design. The 4Ts, HEP, and CPB scores were calculated for each patient. Sensitivity and specificity of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs within receiver operating characteristic (ROC) curves of each score, after which sensitivities and specificities were recalculated. Using standard cut-offs, the sensitivities for the CPB, HEP, and 4Ts scores were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. The AUC of the scoring tool ROC curves were 0.961 for the CPB score, 0.773 for the HEP score, and 0.805 for the 4Ts score. Using the Youden method-derived optimal cut-off of  ≥3 points on the CPB score, sensitivity remained 100% with improved specificity to 88.9%. The CPB score is the preferred HIT clinical scoring tool in adult cardiac surgery patients, whereas the 4Ts score performed less effectively. A cut-off of ≥ 3 points on the CPB score could increase specificity while preserving high sensitivity, which should be validated in a prospective evaluation.

Impact of Postoperative Glycemic Control on Postoperative Morbidity in Patients Undergoing Open Pancreaticoduodenectomy.

OBJECTIVE: To evaluate the impact of postoperative glycemic control on postoperative morbidity in patients undergoing a pancreaticoduodenectomy. METHODS: A retrospective study was performed on patients at The Johns Hopkins Hospital between April 2015 and April 2016. Data were collected on postoperative insulin regimens, blood glucose, rates of hyperglycemia and hypoglycemia, and postoperative complications and were evaluated. RESULTS: Out of 244 patients, 114 (46.7%) experienced at least 1 hyperglycemic (>180 mg/dL) episode and 16 (6.6%) experienced at least 1 hypoglycemic episode (<70 mg/dL) during the first postoperative 24 hours. Early postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of surgical site infections (15.7% vs 7%; P = 0.031). Late postoperative hyperglycemia (>180 mg/dL) was associated with a significantly higher rate of fistulas (4.3% vs 14.6%; P = 0.021). CONCLUSIONS: Early hyperglycemia (>180 mg/dL) is associated with a higher risk of surgical site infections while late hyperglycemia is associated with a higher risk of fistulas. Intensive glucose control (<150 mg/dL) was not demonstrated to decrease the risk of postoperative complications. Similar to other critically ill populations, targeting a glucose goal of <180 mg/dL may be an appropriate target to reduce morbidity without increasing the risk of hypoglycemia.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis.

BACKGROUND: Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 µg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 µg/mL in patients on CVVHD. METHODS: This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state. RESULTS: Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 µg/mL, and 80% of participants have trough concentrations ≥0.60 µg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia. CONCLUSIONS: Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 µg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.

Association of Heparin Dose, Route, Timing, and Duration With Heparin-Induced Thrombocytopenia.

BACKGROUND: The prevalence of heparin-induced thrombocytopenia (HIT) varies by population and the type and duration of heparinoid exposure; however, the association with unfractionated heparin (UFH) dose, route, timing, and duration has not been evaluated in cardiac surgery patients. METHODS: A retrospective case-control study matched HIT-positive adult cardiac surgery patients (positive platelet factor 4 immunoglobulin G and serotonin release assays) 1:1 with HIT-negative controls. Total UFH dose, route, timing, and duration were compared between groups. RESULTS: The study included 124 patients, 92 male (74%), with mean age of 65 ± 11 years. Significantly more HIT-positive patients received intravenous UFH preoperatively or postoperatively compared with patients without HIT (55 [88.7%] vs 23 [37.1%]; P < .001). There were no significant differences regarding intraoperative or subcutaneous UFH dose or duration. When controlling for obesity and cardiopulmonary bypass duration using multivariable conditional logistic regression, the odds of HIT were increased 10-fold in patients who received preoperative or postoperative intravenous UFH continuous infusion (odds ratio 10.2, 95% confidence interval, 3.1 to 33.7; P < .001). Receiver-operating characteristic curves demonstrated that receiving preoperative or postoperative intravenous UFH infusion total dose greater than 32,000 units (sensitivity 82%, specificity 74%, area under the curve 0.78) or longer than 7 hours (sensitivity 87%, specificity 68%, area under the curve 0.77) was associated with HIT. CONCLUSIONS: Odds of HIT were increased 10-fold in adult cardiac surgery patients receiving preoperative or postoperative intravenous UFH infusion. Intraoperative UFH dose and subcutaneous route were not associated with HIT. Future study should evaluate incorporation of intravenous UFH administration, dose, and duration in HIT scoring tools for cardiac surgery patients.

Use and costs of inhaled nitric oxide and inhaled epoprostenol in adult critically ill patients: A quality improvement project.

PURPOSE: Inhaled epoprostenol and inhaled nitric oxide are pulmonary vasodilators commonly used in the management of acute respiratory distress syndrome and right ventricular failure; however, they have vastly different cost profiles. The purpose of the project was to transition from nitric oxide to epoprostenol as the inhaled pulmonary vasodilator (IPV) of choice in adult critically ill patients and evaluate the effect of the transition on associated usage and costs. METHODS: A single-center, prospective, before and after quality improvement project including adult patients receiving inhaled nitric oxide, inhaled epoprostenol, or both was conducted in 7 adult intensive care units, operating rooms, and postanesthesia care units of a tertiary care academic medical center. The total number of patients, hours of therapy, and costs for each agent were compared between stages of protocol implementation and annually. RESULTS: Seven hundred twenty-nine patients received inhaled nitric oxide, inhaled epoprostenol, or both during the study period. The monthly inhaled nitric oxide use in number of patients, hours, and cost decreased during all stages of the project (p < 0.01). The monthly inhaled epoprostenol use in number of patients, hours, and cost increased during all stages (p < 0.01). Overall, total IPV use increased during the study. However, despite this increase in usage, there was a 47% reduction in total IPV cost. CONCLUSION: Implementation of a staged protocol to introduce and expand inhaled epoprostenol use in adult critically ill patients resulted in decreased use and cost of inhaled nitric oxide. The total cost of all IPV was decreased by 47% despite increased IPV use.

Appropriateness of peripheral parenteral nutrition use in adult patients at an academic medical center.

BACKGROUND & AIMS: Current evidence and guidelines identify patient populations who may benefit from parenteral nutrition. Peripheral parenteral nutrition (PPN) may be indicated for a subset of patients; however, PPN therapy carries a risk of associated adverse effects. The purpose of this project was to assess appropriateness of current PPN prescribing practices at an academic medical center to determine whether additional guidance and oversight may be beneficial. METHODS: Adult patients admitted from August 1, 2015 to November 30, 2015 with at least one order of PPN administered were included. PPN use was evaluated for appropriateness using definitions derived from clinical practice guidelines and standard of practice. Adverse events, including phlebitis and bacteremia, were also examined. RESULTS: Of the 159 patients included, 51 (32.1%) received appropriate PPN therapy, in which all four criteria for appropriateness were met. In regards to the criteria for appropriateness, 128 (80.5%) had an appropriate indication, 85 (53.5%) had appropriate time to PPN initiation, 157 (98.7%) had an appropriate duration of therapy, and 112 (70.4%) achieved an appropriate percentage of goal daily calories. In terms of complications associated with PPN therapy, 69 (43.4%) patients had documented phlebitis and bacteremia occurred in 5 (3.1%) of the patients. CONCLUSION: During the study period, PPN was appropriately utilized in only one-third of patients and phlebitis occurred in almost half of all patients. Restrictions on PPN prescribing may allow nutrition support clinicians to prospectively evaluate patients to optimize nutrition therapy and minimize the incidence of inappropriate PPN use.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.

Systemic effects of low-dose dopamine during administration of cytarabine.

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m2/dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Impact of Intraoperative Continuous-Infusion Versus Intermittent Dosing of Cefazolin Therapy on the Incidence of Surgical Site Infections After Coronary Artery Bypass Grafting.

STUDY OBJECTIVES: To determine whether intraoperative continuous-infusion (CI) cefazolin reduces the incidence of surgical site infections (SSIs) compared with intermittent (INT) cefazolin dosing in patients undergoing coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB); safety end points and protocol adherence comparing the two dosing strategies were also explored. DESIGN: Retrospective quasi-experimental (pre-post intervention) cohort study. SETTING: Large academic medical center. PATIENTS: A total of 516 adults who underwent CABG on CPB and received cefazolin intraoperatively between June 1, 2013, and December 31, 2014, were included. The INT cohort included 284 patients who underwent CABG from June 2013 to February 2014. The CI cohort included 232 patients who underwent CABG from April to December 2014, after an intraoperative CI cefazolin protocol for cardiac surgery patients undergoing CPB was adopted in March 2014. MEASUREMENTS AND MAIN RESULTS: The primary end point was incidence of SSIs, and safety end points of renal dysfunction and seizures were evaluated. Multivariable logistic regression analysis was used to determine the impact on SSIs when controlling for other risk factors. A subgroup analysis for this study included 2 months within each time period to evaluate protocol adherence. The overall incidence of SSIs was decreased in patients receiving CI cefazolin, although this did not reach statistical significance (4.6% in the INT cohort vs 1.7% in the CI cohort, p=0.116). Superficial SSIs were significantly reduced in the CI cohort (2.8% in the INT cohort vs 0.4% in the CI cohort, p=0.039). In the regression analysis, CI cefazolin decreased the odds of SSI by 66%, although it did not reach statistical significance (p=0.077). Safety end points were not significantly different between groups. Overall protocol adherence did not differ significantly between the cohorts: 77% in the INT cohort and 67% in the CI cohort (p=0.212). CONCLUSION: CI cefazolin significantly decreased the incidence of superficial SSIs compared with INT cefazolin in patients undergoing CABG on CPB, without increasing the risk for adverse effects. As this study was underpowered to detect a significant difference in overall SSIs, larger, randomized studies are required to validate the superiority of CI cefazolin.

Probiotics and Fecal Microbiota Transplant for Primary and Secondary Prevention of Clostridium difficile Infection.

Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and is associated with an increased risk of mortality. The use of probiotics and fecal microbiota transplantation (FMT) has been studied to reduce the incidence and severity of this infection, but variable efficacy and safety data have been reported. Probiotics are hypothesized to be effective in the management of CDI through a number of mechanisms that include maintenance of normal gastrointestinal flora, antimicrobial and antitoxin properties, and immunomodulatory effects. Despite promising results in small trials and meta-analyses, prospective, randomized, controlled trials have not demonstrated probiotics to be effective in the primary prevention of C. difficile-associated diarrhea (CDAD). Probiotics may be effective for secondary prevention in patients with recurrent CDI, but guidelines acknowledge the lack of compelling evidence. Trials are limited by the use of varying types of strains, numbers of strains, and doses of probiotics, as well the definitions of CDI and CDAD. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent CDI. Current studies have demonstrated minimal adverse effects, with no reports of transmission of infectious diseases; however, the optimal delivery method, sample preparation, and donor selection remain unclear. In this review, findings from recent literature are highlighted, and guideline recommendations for the use of these agents in the primary and secondary prevention of CDI are summarized.

Continuous Intraoperative Cefazolin Infusion May Reduce Surgical Site Infections During Cardiac Surgical Procedures: A Propensity-Matched Analysis.

OBJECTIVES: The authors sought to determine whether an institutional transition from intermittent to continuous dosing of intraoperative antibiotics in cardiac surgery affected surgical site infection (SSI) outcomes. DESIGN: A retrospective chart review utilizing propensity matching. SETTING: A single academic, tertiary care hospital. PARTICIPANTS: One thousand one hundred seventy-nine patients undergoing coronary artery bypass grafting (CABG) and/or cardiac valvular surgery between April 2013 and November 2014 who received perioperative cefazolin. INTERVENTIONS: By method of cefazolin administration, patients were divided into an "intermittent-dosing" (ID) group and a "continuous-infusion" (CI) group. MEASUREMENTS AND MAIN RESULTS: Of the 1,179 patients who underwent cardiac surgery during the study period, 1:1 propensity score matching yielded 399 patients in each group. Rates of diabetes (33.6% ID v 33.8% CI, p = 0.94), coronary artery bypass (62.3% v 61.4%, p = 0.66), and bilateral internal mammary artery harvesting (6.0% v 8.3%, p = 0.22) were similar between groups. SSIs occurred in more ID patients than CI patients (2.3% v 0.5%, p = 0.03). This difference was driven by decreases in extremity and conduit harvest site SSIs (1.8% v 0.3%, p = 0.03), as there were no episodes of mediastinitis, and superficial sternal SSI rates did not differ (0.5% v 0.3%, p = 0.56). There also were significantly fewer episodes of pneumonia in the CI group (6.0% v 2.3%, p = 0.008). Intensive care unit and total lengths of stay did not differ. Thirty-day mortality was 2.8% in both groups (p = 1.00). CONCLUSIONS: As compared to ID regimens, CI cefazolin infusion may reduce post-cardiac surgery infectious complications. Further study in larger patient populations is needed.

Medication management for left ventricular assist device thrombosis.

PURPOSE: Current strategies for prevention and treatment of "pump thrombosis" associated with the use of left ventricular assist devices (LVADs) are discussed. SUMMARY: LVADs provide morbidity, mortality, and quality-of-life benefits in patients with advanced heart failure. Since continuous-flow LVADs came into wide use, there have been increased reports of pump thrombosis (clot formation in the LVAD system that can lead to pump dysfunction and clinical complications). Anticoagulation and antiplatelet therapies are important for preventing pump thrombosis, although the optimal antithrombotic regimen remains unclear. International Normalized Ratio goals should be determined according to specific device characteristics and patient risk factors. Medication therapy for pump thrombosis provides a less invasive option than surgical pump exchange or heart transplantation but is associated with high risks of bleeding events, recurrent pump thrombosis, and mortality. Decisions regarding medical versus surgical management should be based on clinical status and surgical candidacy. Management of pump thrombosis may include intensified i.v. anticoagulation, i.v. or intraventricular thrombolytics, or glycoprotein IIb/IIIa inhibitors. Optimization and close monitoring of anticoagulation and antiplatelet therapy can help reduce the risk of pump thrombosis. CONCLUSION: Intensive clinical and laboratory monitoring are important in identifying signs and symptoms of LVAD thrombosis. Medical management of LVAD thrombosis can be considered an early treatment strategy before thrombi become too large and unresponsive to pharmacotherapies, but antithrombotic medications carry a high risk of bleeding complications and should be used judiciously. More definitive treatment with pump exchange or heart transplantation in appropriate candidates may be required.