Claire V. Murphy

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study

BackgroundThe incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.MethodsA retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher’s exact test while the student’s t-test or Mann–Whitney U test were used for continuous variables.ResultsNinety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (pu2009=u20090.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, pu2009=u20090.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, pu2009=u20090.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, pu2009=u20090.033).ConclusionsAddition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group (P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period (P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Methadone analgesia in the critically ill

PURPOSEnMethadone is increasingly used as an analgesic or a bridge to weaning other analgesics and sedatives in critically ill patients. This review discusses the pharmacology of methadone, summarizes available evidence for its use in the intensive care unit setting, and makes suggestions for appropriate use and monitoring.nnnMATERIALS/METHODSnArticles evaluating the efficacy, safety, and pharmacology of methadone were identified from a PubMed search through June 2015. References from selected articles were reviewed for additional material. Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacology of methadone in critically-ill adults and children were selected.nnnRESULTSnMethadone is a synthetic opioid analgesic with potential advantages over other commonly used opioids. Limited evidence from critically ill pediatric, adult, and burn populations suggests that methadone protocols may expedite weaning opiate infusions, decrease the length of mechanical ventilation, and reduce the incidence of negative outcomes such as opiate withdrawal, delirium, and over-sedation.nnnCONCLUSIONSnData from current literature supports a role for methadone analgesia in weaning opiates and potentially reducing the duration of mechanical ventilation in critically ill patients. More studies are needed to confirm these benefits and determine criteria for patient selection.

Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia

Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4xa0%, adjusted OR 1.15, pu2009=u20090.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5xa0%, pu2009<u20090.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.

Prophylaxis and treatment of venous thromboembolism in the critically ill

Venous thromboembolism (VTE) is a frequent complication in critically ill patients and is associated with increased rates of morbidity and mortality. The use of thromboprophylaxis to reduce the risk of VTE in this patient population is the standard of care. This review will summarize the recommendations set forth in consensus guidelines for the prevention and treatment of VTE across subgroups within the critically ill patient population. In addition, the drug properties of the recommended pharmacologic agents for thromboprophylaxis will be highlighted including their pharmacokinetics, dosing and complications. The critical care practitioner may also encounter novel oral anticoagulants with increasing frequency. These agents will be briefly reviewed in terms of their approved and investigational indications and the clinical concerns related to their use will also be discussed.

Medication-induced and spontaneous hypoglycemia carry the same risk for hospital mortality in critically ill patients☆

PURPOSEnHypoglycemia is associated with increased mortality, but the role of its etiology is unclear. This study aimed to examine the impact of hypoglycemia etiology on mortality risk among critically ill patients.nnnMETHODSnThis single-center, retrospective, cohort study evaluated adult patients admitted to the medical or surgical intensive care unit, who experienced medication-induced or spontaneous hypoglycemia (blood glucose <70 mg/dL) during intensive care unit admission. Patients who became hypoglycemic following receipt of glucose-lowering therapy within a predefined time period were categorized in the medication-induced group. Periods were determined for each agent based on expected pharmacokinetics in critically ill patients. Patients who became hypoglycemic with no identifiable cause were categorized in the spontaneous group. Primary analysis compared medication-induced and spontaneous hypoglycemia with a primary endpoint of all-cause hospital mortality. Secondary analyses stratified patients by diabetes, severity of hypoglycemia, and glycemic variability.nnnRESULTSnA total of 642 patients were eligible for inclusion (305 medication-induced and 337 spontaneous). When adjusted for covariates, no difference in hospital mortality was observed based on hypoglycemia etiology (odds ratio, 1.22 [0.77-1.93]; P=.39). Regardless of etiology, hypoglycemic severity, frequency, and glycemic variability were significantly associated with higher odds of hospital mortality. Hypoglycemic etiology did not impact hospital mortality when patients were stratified by presence or absence of diabetes.nnnCONCLUSIONSnMedication-induced hypoglycemia appears to be equally harmful as spontaneous hypoglycemia during critical illness. Future studies should aim to identify strategies to minimize hypoglycemia regardless of etiology, while also minimizing glycemic variability associated with hypoglycemia treatment.

Impact of late fluid balance on clinical outcomes in the critically ill surgical and trauma population

PURPOSEnManagement of fluid status in critically ill patients poses a significant challenge due to limited literature. This study aimed to determine the impact of late fluid balance management after initial adequate fluid resuscitation on in-hospital mortality for critically ill surgical and trauma patients.nnnMATERIALS AND METHODSnThis single-center retrospective cohort study included 197 patients who underwent surgical procedure within 24 hours of surgical intensive care unit admission. Patients with high fluid balance on postoperative day 7 (>5 L) were compared with those with a low fluid balance (≤5 L) with a primary end point of in-hospital mortality. Subgroup analyses were performed based on diuretic administration, diuretic response, and type of surgery.nnnRESULTSnHigh fluid balance was associated with significantly higher in-hospital mortality (30.2 vs 3%, P<.001) compared with low fluid balance; this relationship remained after multivariable regression analysis. High fluid balance was associated with increased mortality, independent of diuretic administration, diuretic response, and type of surgery.nnnCONCLUSIONSnConsistent with previous literature, high fluid balance on postoperative day 7 was associated with increased in-hospital mortality. Patients who received and responded to diuretic therapy did not demonstrate improved clinical outcomes, which questions their use in the postoperative period.

A clinician's guide to the treatment of foot burns occurring in diabetic patients

INTRODUCTIONnDiabetes mellitus affects 25.8 million Americans and is predicted to almost double by 2050. The presence of diabetes complicates hospital courses because of the microvascular complications associated with disease progression. Patients with diabetes represent 18.3% of annual burn admissions to our unit and 27% have burns to the feet. The purpose of this project was to develop an evidence-based guideline for care of the patient with diabetes and foot burnsnnnMETHODSnA multidisciplinary group was charged with developing an evidence-based guideline for the treatment of foot burns in patients with diabetes. Evidence was evaluated in the areas of diabetes, burn care, hyperbaric medicine, care of diabetic foot wounds and physical therapy. After guideline development and approval, key aspects were incorporated into order sets.nnnRESULTSnKey aspects of this guideline are the ability to identify patients with undiagnosed diabetes, assess diabetic control, optimize glycemic and metabolic control, optimize burn wound management, treat microvascular disease, and provide education and a discharge plan. Evaluated outcomes are glycemic control, length of stay, complication rates, amputation rates, infection rates and the use of hyperbaric oxygen.nnnCONCLUSIONSnBest outcomes for this high risk population will be attainable with an evidence based guideline.

Predictors of Recurrent Hypoglycemia Following a Severe Hypoglycemic Event Among Hospitalized Patients

ABSTRACT Objectives: Severe hypoglycemia is associated with poor hospital outcomes, but variables contributing to the adequacy of treatment have not been described. The objective of this study was to determine predictors of recurrent hypoglycemia among hospitalized patients with a severe hypoglycemic event. Methods: Patients with severe hypoglycemia (glucose <40 mg/dl) with a concomitant insulin order were identified using the study institution’s Information Warehouse. The primary outcome was the prevalence of recurrent hypoglycemia (defined as <70 mg/dl within 24 hours) and to identify independent predictors of recurrent hypoglycemia. Secondary outcomes included time to blood glucose recheck, time to blood glucose ≥70 mg/dl, and rebound hyperglycemia (defined as glucose >300 mg/dl within 24 hours). Multivariable linear and logistic regression models were performed. Results: A total of 129 patients with severe hypoglycemia were identified. The median time to repeat glucose measurement was 29 (IQR 15–61) minutes, while the time to resolution of hypoglycemia was 49 (IQR 26–103) minutes. Recurrent hypoglycemia occurred in 49% of patients, while 19% of patients experienced rebound hyperglycemia. Independent predictors of recurrent hypoglycemia included lower repeat glucose (p = 0.025), low glomerular filtration rate (p = 0.033), and lack of insulin adjustment (p = 0.012). Independent predictors of maximum glucose post-event were type 1 diabetes (p = 0.0003), history of any diabetes (p = 0.013), and total bolus dose of insulin (p < 0.0001). Overnight timing of events was the only predictor of shorter time to hypoglycemia resolution (p < 0.0001). Conclusions: Recurrent hypoglycemia following severe hypoglycemia is common in the hospital, suggesting the need for enhanced monitoring in such patients. Further research is needed to identify methods to reduce the incidence of recurrent hypoglycemia.

Impact of Serum Phosphate in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock

Background: Hypo- and hyperphosphatemia are common in severe sepsis and septic shock. Published outcome data in patients with phosphate derangements primarily focus on hypophosphatemia and the general critically ill population. This study aimed to determine the impact of serum phosphate on clinical outcomes in patients with severe sepsis and septic shock. Methods: A retrospective cohort analysis of adult mechanically ventilated patients with severe sepsis or septic shock was performed. Patients were randomly selected from an internal intensive care unit (ICU) database at an academic medical center in the United States and screened for inclusion and exclusion criteria. Time-weighted phosphate was calculated using all phosphate measurements obtained during ICU admission. The associations between time-weighted phosphate and duration of mechanical ventilation, 28-day mortality, and ICU and hospital length of stay were evaluated using linear or logistic regression as appropriate. Results: One-hundred ninety-seven patients were evaluated: 33 were categorized as hypophosphatemia, 123 as normophosphatemia, and 41 as hyperphosphatemia. Patients with time-weighted hyperphosphatemia had a higher Simplified Acute Physiology Score III score and incidence of septic shock. Significantly higher rates of 28-day mortality were observed among those with time-weighted phosphate levels above 3.5 mg/dL. However, both time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. For every 0.5 mg/dL increase in time-weighted phosphate referent values from 4.0 to 6.0, the duration of mechanical ventilation decreased by 8% to 26%. For every 0.5 mg/dL decrease in time-weighted phosphate referent values from 3.0 to 1.0, significant decreases in duration of mechanical ventilation ranged from 14% to 41%. Conclusion: Time-weighted hyperphosphatemia may be associated with increased mortality in mechanically ventilated patients with severe sepsis or septic shock. However, time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. Future studies should further describe the impact of hypo- and hyperphosphatemia on clinical outcomes among critically ill patients with severe sepsis or septic shock.