Ketamine/propofol admixture (ketofol) at induction in the critically ill against etomidate (KEEP PACE trial): study protocol for a randomized controlled trial.

BACKGROUND: Endotracheal intubation (ETI) is commonly performed as a life-saving procedure in the intensive care unit (ICU). It is often associated with significant hemodynamic perturbations and can severely impact the outcome of ICU patients. Etomidate is often chosen by many critical care providers for the patients who are hypotensive because of its superior hemodynamic profile compared to other induction medications. However, recent evidence has raised concerns about the increased incidence of adrenal insufficiency and mortality associated with etomidate use. A combination of ketamine and propofol (known as ketofol) has been studied in various settings as an alternative induction agent. In recent years, studies have shown that this combination may provide adequate sedation while maintaining hemodynamic stability, based on the balancing of the hemodynamic effects of these two individual agents. We hypothesized that ketofol may offer a valuable alternative to etomidate in critically ill patients with or without hemodynamic instability. METHODS/DESIGN: A randomized controlled parallel-group clinical trial of adult critically ill patients admitted to either a medical or surgical ICU at Mayo Clinic in Rochester, MN will be conducted. As part of planned emergency research, informed consent will be waived after appropriate community consultation and notification. Patients undergoing urgent or emergent ETI will receive either etomidate or a 1:1 admixture of ketamine and propofol (ketofol). The primary outcome will be hemodynamic instability during the first 15 minutes following drug administration. Secondary outcomes will include ICU length of stay, mortality, adrenal function, ventilator-free days and vasoactive medication use, among others. The planned sample size is 160 total patients. DISCUSSION: The overall goal of this trial is to assess the hemodynamic consequences of a ketamine-propofol combination used in critically ill patients undergoing urgent or emergent ETI compared to etomidate, a medication with an established hemodynamic profile. The trial will address a crucial gap in the literature regarding the optimal induction agent for ETI in patients that may have potential or established hemodynamic instability. Greater experience with planned emergency research will, hopefully, pave the way for future prospective randomized clinical trials in the critically ill population. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02105415. 31 March 2014.

Ketamine and propofol combination ("ketofol") for endotracheal intubations in critically ill patients: a case series.

BACKGROUND: Endotracheal intubation is a common procedure performed for critically ill patients that can have immediate life-threatening complications. Induction medications are routinely given to facilitate the procedure, but most of these medications are associated with hypotension. While etomidate is known for its neutral hemodynamic profile, it has been linked with increased mortality in septic patients and increased morbidity in trauma patients. Ketamine and propofol are effective anesthetics with counteracting cardiovascular profiles. No data are available about the use of this combination in critically ill patients undergoing endotracheal intubation. CASE REPORT: We describe 6 cases in which the combination of ketamine and propofol ("ketofol") was used as an induction agent for endotracheal intubation in critically ill patients with a focus on hemodynamic outcomes. All patients received a neuromuscular blocker and fentanyl, while 5 patients received midazolam. We recorded mean arterial pressure (MAP) 1 minute before induction and 15 minutes after intubation with the combination. Of the 6 patients, 5 maintained a MAP ≥ 65 mmHg 15 minutes after intubation. One patient was on norepinephrine infusion with a MAP of 64 mmHg, and did not require an increase in the dose of the vasopressor 15 minutes after intubation. No hemodynamic complications were reported after any of the intubations. CONCLUSIONS: This case series describes the use of the "ketofol" combination as an induction agent for intubation in critically ill patients when hemodynamic stability is desired. Further research is needed to establish the safety of this combination and how it compares to other induction medications.

Transfusion-Related Acute Lung Injury After IVIG for Myasthenic Crisis.

BACKGROUND: A 26-year-old female with myasthenic crisis developed transfusion-related acute lung injury (TRALI) after she was treated with intravenous immunoglobulin. METHODS: Case report. RESULTS: Respiratory status markedly worsened with each intravenous immunoglobulin (IVIG) administration and progressing from a need to use bilevel positive airway pressure (BiPAP) to intubation. Pulmonary function tests improved during this episode. CONCLUSIONS: IVIG may cause TRALI and due to subtle clinical findings can be mistaken for neuromuscular respiratory failure.

A quality improvement project sustainably decreased time to onset of active physical therapy intervention in patients with acute lung injury.

RATIONALE: Rehabilitation started early during an intensive care unit (ICU) stay is associated with improved outcomes and is the basis for many quality improvement (QI) projects showing important changes in practice. However, little evidence exists regarding whether such changes are sustainable in real-world practice. OBJECTIVES: To evaluate the sustained effect of a quality improvement project on the timing of initiation of active physical therapy intervention in patients with acute lung injury (ALI). METHODS: This was a pre-post evaluation using prospectively collected data involving consecutive patients with ALI admitted pre-quality improvement (October 2004-April 2007, n = 120) versus post-quality improvement (July 2009-July 2012, n = 123) from a single medical ICU. MEASUREMENTS AND MAIN RESULTS: The primary outcome was time to first active physical therapy intervention, defined as strengthening, mobility, or cycle ergometry exercises. Among ICU survivors, more patients in the post-quality improvement versus pre-quality improvement group received physical therapy in the ICU (89% vs. 24%, P < 0.001) and were able to stand, transfer, or ambulate during physical therapy in the ICU (64% vs. 7%, P < 0.001). Among all patients in the post-quality improvement versus pre-quality improvement group, there was a shorter median (interquartile range) time to first physical therapy (4 [2, 6] vs. 11 d [6, 29], P < 0.001) and a greater median (interquartile range) proportion of ICU days with physical therapy after initiation (50% [33, 67%] vs. 18% [4, 47%], P = 0.003). In multivariable regression analysis, the post-quality improvement period was associated with shorter time to physical therapy (adjusted hazard ratio [95% confidence interval], 8.38 [4.98, 14.11], P < 0.001), with this association significant for each of the 5 years during the post-quality improvement period. The following variables were independently associated with a longer time to physical therapy: higher Sequential Organ Failure Assessment score (0.93 [0.89, 0.97]), higher FiO2 (0.86 [0.75, 0.99] for each 10% increase), use of an opioid infusion (0.47 [0.25, 0.89]), and deep sedation (0.24 [0.12, 0.46]). CONCLUSIONS: In this single-site, pre-post analysis of patients with ALI, an early rehabilitation quality improvement project was independently associated with a substantial decrease in the time to initiation of active physical therapy intervention that was sustained over 5 years. Over the entire pre-post period, severity of illness and sedation were independently associated with a longer time to initiation of active physical therapy intervention in the ICU.

Chronic pulmonary aspergillosis complicating bronchial atresia.

Bronchial atresia is a rare pulmonary developmental anomaly characterized by the presence of a focal obliteration of a segmental or lobar bronchial lumen. The lung distal to the atretic bronchus is typically emphysematous along with the presence of mucus filled ectatic bronchi (mucoceles). BA is usually asymptomatic but pulmonary infections can rarely develop in the emphysematous lung distal to the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis (CPA) in a patient with BA with no evidence of immune dysfunction. The patient was treated initially with voriconazole and subsequently underwent surgical excision of the involved area. On follow-up, she has done extremely well with no evidence for recurrence. In summary, we describe the first case of chronic pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.

Physical rehabilitation of patients in the intensive care unit requiring extracorporeal membrane oxygenation: a small case series.

BACKGROUND AND PURPOSE: Neuromuscular weakness and impaired physical function are common and long-lasting complications experienced by intensive care unit (ICU) survivors. There is growing evidence that implementing rehabilitation therapy shortly after ICU admission improves physical function and reduces health care utilization. Recently, there is increasing interest and utilization of extracorporeal membrane oxygenation (ECMO) to support patients with severe respiratory failure. Patients receiving ECMO are at great risk for significant physical impairments and pose unique challenges for delivering rehabilitation therapy. Consequently, there is a need for innovative examples of safely and feasibly delivering active rehabilitation to these patients. CASE DESCRIPTION: This case report describes 3 patients with respiratory failure requiring ECMO who received physical rehabilitation to illustrate and discuss relevant feasibility and safety issues. OUTCOMES: In case 1, sedation and femoral cannulation limited rehabilitation therapy while on ECMO. In the 2 subsequent cases, minimizing sedation and utilizing a single bicaval dual lumen ECMO cannula placed in the internal jugular vein allowed patients to be alert and participate in active physical therapy while on ECMO, illustrating feasible rehabilitation techniques for these patients. DISCUSSION: Although greater experience is needed to more fully evaluate the safety of rehabilitation on ECMO, these initial cases are encouraging. We recommend systematically and prospectively tracking safety events and patient outcomes during rehabilitation on ECMO to provide greater evidence in this area.