Tyree Kiser

Erythromycin vs Metoclopramide for Facilitating Gastric Emptying and Tolerance to Intragastric Nutrition in Critically Ill Patients

BACKGROUND The purpose of this study is to evaluate erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric enteral nutrition (EN). METHODS Twenty critically ill patients with a gastric residual >150 mL while receiving EN were randomized to receive 4 intravenous doses of erythromycin 250 mg or metoclopramide 10 mg, each administered every 6 hours. Acetaminophen 975 mg was administered enterally at baseline and after the fourth dose. Acetaminophen peak plasma concentration (Cmax), concentration at 60 minutes (C(60)), time to Cmax (Tmax), and area under the concentration-time curve from 0 to 60 minutes (AUC(0-60)) were determined. Residual volumes and feeding rates were recorded. RESULTS Compared with baseline, erythromycin increased Cmax (9.5 +/- 6.1 mg/L to 17.7 +/- 11.9 mg/L, P < .01), C(60) (5.4 +/- 3.5 mg/L to 12.9 +/- 7.6 mg/L, P < .01), and AUC(0-60) (3.5 +/- 3.0 mg.h/L to 12.5 +/- 8.7 mg.h/L, P < .01), while metoclopramide increased only AUC(0-60) (4.4 +/- 2.8 mg.h/L to 9.5 +/- 3.8 mg.hr/L, P < .05). Neither agent significantly reduced Tmax. Both erythromycin and metoclopramide reduced residual volumes (122 +/- 48 mL to 36 +/- 48 mL, P < .01, and 103 +/- 88 mL to 21 +/- 23 mL, P < .05, respectively) and allowed increased feeding rates (17 +/- 23 mL/h to 45 +/- 21 mL/h, P < .05, and 14 +/- 17 mL/h to 44 +/- 22 mL/h, P < .05, respectively). CONCLUSIONS Both agents facilitate tolerance to intragastric EN, but erythromycin may be more effective than metoclopramide for enhancing gastric motility.

Gastric Motility Function in Critically Ill Patients Tolerant vs Intolerant to Gastric Nutrition

BACKGROUND Administration of gastric enteral nutrition (EN) in the intensive care unit (ICU) is commonly impeded by high gastric residual volumes (GRV). This study evaluated gastric emptying in patients with limited GRV (tolerant group) vs volumes > or =150 mL (intolerant group) and whether prokinetic therapy improves gastric motility in intolerant patients. METHODS To assess gastric motility, mechanically ventilated patients received acetaminophen 975 mg, and peak plasma concentration (Cmax), concentration at 60 minutes (C(60)), time to Cmax (Tmax), and area under the concentration-time curve from 0 to 60 minutes (AUC(0-60)) were determined. This evaluation was repeated in intolerant patients after 24 hours of either erythromycin 250 mg or metoclopramide 10 mg therapy, both administered intravenously every 6 hours. RESULTS Ten tolerant and 20 intolerant patients were studied. Tolerant patients had significantly greater Cmax (14.12 +/- 7.25 vs 9.28 +/- 5.22 mg/L; p < .05), C(60) (9.62 +/- 4.65 vs 6.08 +/- 4.00 mg/L; p < .001), and AUC(0-60) (10.01 +/- 5.97 vs 3.93 +/- 2.84 mg/h/L; p < .01) and shortened Tmax (0.81 +/- 0.61 vs 1.98 +/- 1.26 hours; p < .001) compared with intolerant patients. After prokinetic therapy, Cmax (15.26 +/- 8.85 mg/L), C(60) (11.96 +/- 5.99 mg/L), and AUC(0-60) (10.90 +/- 6.57 mg/h/L) increased and Tmax (1.07 +/- 1.01 hours) decreased in the intolerant group to values similar to the tolerant group. CONCLUSIONS ICU patients with elevated GRV during gastric EN have delayed gastric motility. Initiating prokinetic therapy accelerates gastric emptying to resemble that of ICU patients tolerating EN.

Safety, Efficacy, and Dosing Requirements of Bivalirudin in Patients with Heparin‐Induced Thrombocytopenia

Study Objective. To evaluate the safety, efficacy, and dosing requirements of bivalirudin in patients with heparin‐induced thrombocytopenia (HIT).

A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal.

Objectives:To evaluate dexmedetomidine as adjunctive therapy to lorazepam for severe alcohol withdrawal. Design:Prospective, randomized, double-blind, placebo-controlled trial. Setting:Single center; medical ICU. Patients:Twenty-four adult patients with a Clinical Institute Withdrawal Assessment score greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour period. Interventions:Patients received a symptom-triggered Clinical Institute Withdrawal Assessment protocol with lorazepam and were randomized to dexmedetomidine 1.2 &mgr;g/kg/hr (high dose), 0.4 &mgr;g/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms. Measurement and Main Results:High-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship. The difference in 24-hour lorazepam requirements after versus before study drug was greater in the dexmedetomidine group compared with the placebo group (–56 mg vs –8 mg, p = 0.037). Median differences were similar for high dose and low dose. The 7-day cumulative lorazepam requirements were not statistically different between dexmedetomidine and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores representing severe agitation (13% vs 25%) or moderate agitation (27% vs 22%) within 24 hours of initiating study drug were similar for dexmedetomidine and placebo groups, respectively. Bradycardia occurred more frequently in the dexmedetomidine group versus placebo group (25% vs 0%, p = not significant), with the majority of bradycardia occurring in the high-dose group (37.5%). Study drug rate adjustments occurred more often in the dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02). Neither endotracheal intubation nor seizure occurred in any group while on study drug. Conclusions:Adjunctive dexmedetomidine for severe alcohol withdrawal maintains symptom control and reduces lorazepam exposure in the short term, but not long term, when using a symptom-triggered protocol. Monitoring for bradycardia is needed with dexmedetomidine but the occurrence may be lessened with low dose. Further study is needed to evaluate the clinical impact of dexmedetomidine.

Adjunctive Dexmedetomidine Therapy in the Intensive Care Unit: A Retrospective Assessment of Impact on Sedative and Analgesic Requirements, Levels of Sedation and Analgesia, and Ventilatory and Hemodynamic Parameters

Study Objective. To determine if adjunctive dexmedetomidine therapy in intensive care patients alters requirements for and levels of sedation and analgesia, and to describe hemodynamic and ventilatory parameters.

Outcomes Associated with Corticosteroid Dosage in Critically Ill Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease

RATIONALE Studies evaluating corticosteroid (CS) dosing for patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have largely excluded patients admitted directly to the intensive care unit (ICU), and none have evaluated the effect of CS dosing regimens on mortality. OBJECTIVES To examine the effectiveness and safety of lower- versus high-dose CS in patients admitted to the ICU with an AECOPD. METHODS This pharmacoepidemiologic cohort study evaluated ICU patients with AECOPD admitted to one of 473 hospitals and treated with CS within the first 2 days between January 1, 2003 and December 31, 2008. Patients were grouped into lower-dose (methylprednisolone, ≤240 mg/d) or high-dose (methylprednisolone, >240 mg/d) groups based on CS dosage on hospital Day 1 or 2. The primary outcome was hospital mortality. MEASUREMENTS AND MAIN RESULTS A total of 17,239 patients were included; 6,156 (36%) were in the lower-dose and 11,083 (64%) in the high-dose CS group. After propensity score matching and adjustment for unbalanced covariates, lower-dose CS was not associated with a significant reduction in mortality (odds ratio, 0.85; 95% confidence interval [CI], 0.71-1.01; P = 0.06), but it was associated with reduced hospital (-0.44 d; 95% CI, -0.67 to -0.21; P < 0.01) and ICU (-0.31 d; 95% CI, -0.46 to -0.16; P < 0.01) length-of-stay, hospital costs (-

Propylene Glycol Accumulation in Critically Ill Patients Receiving Continuous Intravenous Lorazepam Infusions

2,559; 95% CI, -

Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

4,508 to -

Efflux Pump Contribution to Multidrug Resistance in Clinical Isolates of Pseudomonas aeruginosa

609; P = 0.01), length of invasive ventilation (-0.29 d; 95% CI, -0.52 to -0.06; P = 0.01), need for insulin therapy (22.7% vs. 25.1%; P < 0.01), and fungal infections (3.3% vs. 4.4%; P < 0.01). CONCLUSIONS Two-thirds of patients admitted to the ICU with an AECOPD are treated with high doses of CS that are associated with worse outcomes and more frequent adverse effects. Lower dosage strategies should be encouraged for patients admitted to the ICU and the optimum dose should be determined through clinical trials.

Severe acute exacerbations of chronic obstructive pulmonary disease: does the dosage of corticosteroids and type of antibiotic matter?

Background: Lorazepam is recommended by the Society of Critical Care Medicine as the preferred agent for sedation of critically ill patients. Intravenous lorazepam contains propylene glycol, which has been associated with toxicity when high doses of lorazepam are administered. Objective: To evaluate the accumulation of propylene glycol in critically ill patients receiving lorazepam by continuous infusion and determine factors associated with propylene glycol concentration. Methods: A 6-month, retrospective, safety assessment was conducted of adults admitted to the medical intensive care unit who were receiving lorazepam by continuous infusion for 12 hours or more. Propylene glycol serum concentrations were obtained 24–48 hours after continuous-infusion lorazepam was initiated and every 3–5 days thereafter. Propylene glycol accumulation was defined as concentrations of 25 mg/dL or more. Groups with and without propylene glycol accumulation were compared and factors associated with propylene glycol concentration were determined using multivariate correlation regression analyses. Results: Forty-eight propylene glycol serum samples were obtained from 33 patients. Fourteen (42%) patients had propylene glycol accumulation, representing 23 (48%) serum samples. Univariate analyses showed the following factors were related to propylene glycol accumulation: baseline renal dysfunction, presence of alcohol withdrawal, sex, age, Acute Physiology and Chronic Health Evaluation (APACHE II) score, rate of lorazepam continuous infusion, and 24-hour lorazepam dose. Multivariate linear regression modeling demonstrated that propylene glycol concentration was strongly associated with the continuous infusion rate and 24-hour dose (adjusted r2 ≥0,77; p < 0.001). Independent correlation analyses showed that these 2 variables were so strongly associated with propylene glycol concentration (r2 ≥0.71; p < 0.001) that they alone predicted propylene glycol concentration. Seven (21%) patients developed renal dysfunction after continuous-infusion lorazepam was initiated, but associated causes were indeterminable. Other possible propylene glycol-associated adverse effects were not observed. Conclusions: The continuous infusion rate and cumulative 24-hour lorazepam dose are strongly associated with and independently predict propylene glycol concentrations. Despite the absence of confirmed propylene glycol-associated adverse effects, clinicians should be aware that propylene glycol accumulation may occur with continuous-infusion lorazepam.