A Multicenter Evaluation of Outcomes Following the Use of Nebulized Heparin for Inhalation Injury (HIHI2 Study).

Inhalation injury causes significant morbidity and mortality secondary to compromise of the respiratory system as well as systemic effects limiting perfusion and oxygenation. Nebulized heparin reduces fibrin cast formation and duration of mechanical ventilation in patients with inhalation injury. To date, no study has compared both dosing strategies of 5000 and 10,000 units to a matched control group. This multicenter, retrospective, case-control study included adult patients with bronchoscopy-confirmed inhalation injury. Each control patient, matched according to age and percent of total body surface area, was matched to a patient who received 5000 units and a patient who received 10,000 units of nebulized heparin. The primary endpoint of the study was duration of mechanical ventilation. Secondary endpoints included 28-day mortality, ventilator-free days in the first 28 days, difference in lung injury scores, length of hospitalization, incidence of ventilator-associated pneumonia, and rate of major bleeding. Thirty-five matched patient trios met inclusion criteria. Groups were well-matched for age (P = .975) and total body surface area (P = .855). Patients who received nebulized heparin, either 5000 or 10,000 units, had 8 to 11 less days on the ventilator compared to controls (P = .001). Mortality ranged from 3 to 14% overall and was not statistically significant between groups. No major bleeding events related to nebulized heparin were reported. Mechanical ventilation days were significantly decreased in patients who received 5000 or 10,000 units of nebulized heparin. Nebulized heparin, either 5000 units or 10,000 units, is a safe and effective treatment for inhalation injury.

Major publications in the critical care pharmacotherapy literature: January-December 2017.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2017. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 115 during 2017. Two meta-analyses and eight original research trials were reviewed here from those included in the monthly CCPLU. Meta-analyses on early, goal-directed therapy for septic shock and statin therapy for acute respiratory distress syndrome were summarized. Original research trials that were included evaluate thrombolytic therapy in severe stroke, hyperoxia and hypertonic saline in septic shock, intraoperative ketamine for prevention of post-operative delirium, intravenous ketorolac dosing regimens for acute pain, angiotensin II for vasodilatory shock, dabigatran reversal with idarucizumab, bivalirudin versus heparin monotherapy for myocardial infarction, and balanced crystalloids versus saline fluid resuscitation. CONCLUSION: This clinical review provides perspectives on impactful critical care pharmacotherapy publications in 2017.

Outcomes Following the Use of Nebulized Heparin for Inhalation Injury (HIHI Study).

Inhalation injury (IHI) causes significant morbidity and mortality in burn victims due to both local and systemic effects. Nebulized heparin promotes improvement in lung function and decreased mortality in IHI by reducing the inflammatory response and fibrin cast formation. The study objective was to determine if nebulized heparin 10,000 units improves lung function and decreases mechanical ventilation duration, mortality, and hospitalization length in IHI with minimal systemic adverse events. This retrospective, case-control study evaluated efficacy and safety of nebulized heparin administered to mechanically ventilated adults admitted within 48 hr of confirmed IHI. Nebulized heparin 10,000 units was administered Q4H for 7 days, or until extubation if sooner, alternating with albuterol and a mucolytic. Patients were matched on a case-by-case basis based on percent TBSA burn and age to patients from a historical group with IHI before heparin protocol implementation. The primary outcome was duration of mechanical ventilation. Secondary outcomes included lung injury score, ventilator-free days during the first 28 days, 28-day mortality, hospitalization length, ventilator-associated pneumonia incidence, bronchoscopy incidence, and bleeding events. Data were collected in 72 patients, 36 of which received nebulized heparin and 36 historical controls. Two patients from the heparin group and three patients from the control group died/were discharged while on the ventilator. Data were analyzed separately with 1) all subjects included and 2) with subjects who died/were discharged on the ventilator excluded. In the latter comparison, patients receiving nebulized heparin demonstrated a statistically significant decrease in median (interquartile range) duration of initial mechanical ventilation compared with controls [7.0 (4.0, 13.5) vs. 14.5 (5.3, 22.3) days; P = .044]. Patients in the heparin group had a significantly increased number of median (interquartile range) ventilator-free days in the first 28 days [21.0 (14.5-24.0) vs 13.5 (4.3-22.8) days; P = .031]. There were no differences in hospitalization length, lung injury score during the first 7 days post injury, 28-day mortality, ventilator-associated pneumonia rate, or bleeding events. Nebulized heparin 10,000 units in conjunction with a beta-agonist and mucolytic produced a significant decrease in duration of mechanical ventilation and increase in ventilator-free days in adult patients with IHI. Nebulized heparin was safe and did not result in an increase in bleeding events. To our knowledge, this is the first case-control study with matched cohorts based on age and %TBSA which are significant factors contributing to morbidity and mortality in IHI.

Transition From Intravenous to Subcutaneous Insulin in Critically Ill Adults.

BACKGROUND: Glycemic control decreases morbidity and mortality in critically ill patients. However, limited guidance exists regarding the transition from intravenous (IV) to subcutaneous insulin therapy. A validated protocol for transition is necessary since glycemic variability, hyperglycemia, and hypoglycemia adversely impact patient outcomes. METHOD: The objective was to determine the safest and most effective method to transition critically ill adults from IV to subcutaneous insulin. This single-center, retrospective, observational study included adults admitted to the burn, medical, or surgical/trauma intensive care units from January 1, 2011, to September 30, 2014. A computer-based program provided a reflection of the patient's total daily IV insulin requirements. This information was then utilized to stratify patients into groups according to their initial dose of subcutaneous insulin as a percentage of the prior 24-hour IV requirements (group stratification: 0-49%, 50-59%, 60-69%, 70-79%, ≥80%). The primary endpoint was the percentage of blood glucose (BG) concentrations within target range (70-150 mg/dL) 48 hours following transition. RESULTS: One hundred patients with 1394 BG concentrations were included. The 50-59% group achieved the highest rate of BG concentrations in goal range (68%) (P < .001). The 0-49% group, which was the transition method utilized most often, resulted in the lowest rate of goal achievement (46%). CONCLUSIONS: This retrospective study suggests critically ill adults may be safely transitioned to 50-59% of their 24-hour IV insulin requirements. A dosing protocol will be implemented to transition to 50-70% subcutaneous insulin. Follow-up data will be reviewed to assess the protocol's safety and efficacy.

Impact of Quetiapine Treatment on Duration of Hypoactive Delirium in Critically Ill Adults: A Retrospective Analysis.

STUDY OBJECTIVE: Because delirium remains a common consequence of critical illness, and reducing its duration has been shown to have a positive impact on patient outcomes during and after an intensive care unit (ICU) stay, we sought to determine whether treatment of hypoactive delirium with quetiapine reduces the duration of delirium compared with no pharmacologic treatment. DESIGN: Retrospective cohort study. SETTING: Three medical-surgical ICUs within the two main campuses of an academic tertiary care hospital system. PATIENTS: A total of 113 adults with documented hypoactive delirium during an ICU length of stay (LOS) of at least 72 hours between August 2013 and September 2014; 52 patients received at least one dose of quetiapine during their hypoactive delirium course, and 61 patients received no pharmacologic delirium treatment. MEASUREMENTS AND MAIN RESULTS: Patients were screened for hypoactive delirium using the Confusion Assessment Method-ICU (CAM-ICU) and the Richmond Agitation Sedation Scale (RASS). The primary outcome was time to first resolution of delirium, and secondary outcomes included ICU and hospital LOS, and duration of mechanical ventilation. To assess potential adverse effects of quetiapine, the number of RASS assessments deeper than goal and the total number of RASS assessments documented during the delirium course were recorded for all patients. Daily progress notes and discharge documentation were surveyed to assess for new onset of extrapyramidal symptoms or torsade de pointes. Median duration of hypoactive delirium was shorter in the quetiapine-treated group compared with the no-quetiapine group (1.5 vs 2.0 days, p=0.04), and time to extubation after screening positive for delirium trended favorably toward quetiapine-treated patients (3 vs 5 days, p=0.08). There were no significant differences in ICU or hospital LOS, and safety outcomes were similar between groups. CONCLUSION: In this mixed ICU population, treatment of hypoactive delirium with quetiapine was safe and reduced the duration of delirium compared with standard care alone. Prospective placebo-controlled studies are needed to further assess the role of antipsychotics in hypoactive delirium.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

PURPOSE: Ten recently published articles with important implications for critical care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of ß-lactam antibiotics in severe sepsis. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.