Joanna L. Stollings

Rapid-Sequence Intubation A Review of the Process and Considerations When Choosing Medications

Objective: To summarize published data regarding the steps of rapid-sequence intubation (RSI); review premedications, induction agents, neuromuscular blockers (NMB), and studies supporting use or avoidance; and discuss the benefits and deficits of combinations of induction agents and NMBs used when drug shortages occur. Data Source: A search of Medline databases (1966–October 2013) was conducted. Study Selection and Data Extraction: Databases were searched using the terms rapid-sequence intubation, fentanyl, midazolam, atropine, lidocaine, phenylephrine, ketamine, propofol, etomidate thiopental, succinylcholine, vecuronium, atracurium, and rocuronium. Citations from publications were reviewed for additional references. Data Synthesis: Data were reviewed to support the use or avoidance of premedications, induction agents, and paralytics and combinations to consider when drug shortages occur. Conclusions: RSI is used to secure a definitive airway in often uncooperative, nonfasted, unstable, and/or critically ill patients. Choosing the appropriate premedication, induction drug, and paralytic will maximize the success of tracheal intubation and minimize complications.

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown. Objectives: To pilot a cluster‐randomized, multiple‐crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids. Methods: This was a cluster‐randomized, multiple‐crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringers solution or Plasma‐Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction. Measurements and Main Results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500‐3,377] vs. 1,617 ml [500‐3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98). Conclusions: An electronic health record‐embedded, cluster‐randomized, multiple‐crossover trial comparing saline with balanced crystalloids can produce well‐balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Balanced Crystalloids versus Saline in Critically Ill Adults

BACKGROUND Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS We conducted a single‐center, pragmatic, multiple‐crossover trial comparing balanced crystalloids (lactated Ringers solution or Plasma‐Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16‐month trial. The primary outcome was hospital‐free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days — a composite of death from any cause, new renal‐replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital‐free days did not differ between the balanced‐crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01). CONCLUSIONS Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital‐free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT‐ED ClinicalTrials.gov number, NCT02614040.)

A Clinic Model: Post-Intensive Care Syndrome and Post-Intensive Care Syndrome-Family.

ABSTRACT The number of patients surviving critical illness in the United States has increased with advancements in medicine. Post‐intensive care syndrome and post‐intensive care syndrome‐family are terms developed by the Society of Critical Care Medicine in order to address the cognitive, psychological, and physical sequelae emerging in patients and their families after discharge from the intensive care unit. In the United Kingdom and Europe, intensive care unit follow‐up clinics have been used to address the complications of post‐intensive care syndrome for some time. However, the interprofessional clinic at Vanderbilt University Medical Center is among the first in the United States to address the wide variety of problems experienced by intensive care survivors and to provide patients and their families with care after discharge from the intensive care unit.

Antipsychotic prescribing patterns during and after critical illness: a prospective cohort study.

BackgroundAntipsychotics are used to treat delirium in the intensive care unit (ICU) despite unproven efficacy. We hypothesized that atypical antipsychotic treatment in the ICU is a risk factor for antipsychotic prescription at discharge, a practice that might increase risk since long-term use is associated with increased mortality.MethodsAfter excluding patients on antipsychotics prior to admission, we examined antipsychotic use in a prospective cohort of ICU patients with acute respiratory failure and/or shock. We collected data on medication use from medical records and assessed patients for delirium using the Confusion Assessment Method for the ICU. Using multivariable logistic regression, we analyzed whether age, delirium duration, atypical antipsychotic use, and discharge disposition (each selected a priori) were independent risk factors for discharge on an antipsychotic. We also examined admission Acute Physiology and Chronic Health Evaluation (APACHE) II score, haloperidol use, and days of benzodiazepine use in post hoc analyses.ResultsAfter excluding 18 patients due to prior antipsychotic use and three who withdrew, we included 500 patients. Among 208 (42%) treated with an antipsychotic, median (interquartile range) age was 59 (49–69) years and APACHE II score was 26 (22–32), characteristics that were similar among antipsychotic nonusers. Antipsychotic users were more likely than nonusers to have had delirium (93% vs. 61%, p < 0.001). Of the 208 antipsychotic users, 172 survived to hospital discharge, and 42 (24%) of these were prescribed an antipsychotic at discharge. Treatment with an atypical antipsychotic was the only independent risk factor for antipsychotic prescription at discharge (odds ratio 17.6, 95% confidence interval 4.9 to 63.3; p < 0.001). Neither age, delirium duration, nor discharge disposition were risk factors (p = 0.11, 0.38, and 0.12, respectively) in the primary regression model, and post hoc analyses found APACHE II (p = 0.07), haloperidol use (p = 0.16), and days of benzodiazepine use (p = 0.31) were also not risk factors for discharge on an antipsychotic.ConclusionsIn this study, antipsychotics were used to treat nearly half of all antipsychotic-naïve ICU patients and were prescribed at discharge to 24% of antipsychotic-treated patients. Treatment with an atypical antipsychotic greatly increased the odds of discharge with an antipsychotic prescription, a practice that should be examined carefully during medication reconciliation since these drugs carry “black box warnings” regarding long-term use.

Pharmacist Leadership in ICU Quality Improvement Coordinating Spontaneous Awakening and Breathing Trials

Background: Coordinating efforts across disciplines in the intensive care unit is a key component of quality improvement (QI) efforts. Spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) are considered key components of guidelines, yet unfortunately are often not done or coordinated properly. Objective: To determine if a pharmacist-driven awakening and breathing coordination (ABC) QI program would improve compliance (ie, process measures) as compared with the previous protocol, which did not involve pharmacists. Methods: The QI program included pharmacist-led education, daily discussion on rounds, and weekly performance reports to staff. Using a pre-QI versus during-QI versus post-QI intervention design, we compared data from 500 control ventilator-days (pre-QI period) versus 580 prospective ventilator-days (during-QI period). We then evaluated the sustainability of the QI program in 216 ventilator-days in the post-QI period. Results: SAT safety screens were performed on only 20% pre-QI patient-days versus 97% of during-QI patient-days (P < 0.001) and 100% of post-QI patient-days (P = 0.25). The rates of passing the SAT safety screen in pre-QI and during-QI periods were 63% versus 78% (P = 0.03) and 81% in the post-QI period (P = 0.86). The rates of SATs among eligible patients on continuous infusions were only 53% in the pre-QI versus 85% in the during-QI (P = 0.0001) and 87% in the post-QI (P = 1) periods. Conclusions: In this QI initiative, a pharmacist-driven, interdisciplinary ABC protocol significantly improved process measures compliance, comparing the pre-QI versus during-QI rates of screening, performing, and coordinating SAT and SBTs, and these results were sustained in the 8-month follow-up period post-QI program.

Fosfomycin for Multidrug Treatment of Klebsiella pneumoniae Carbapenemase Bacteremia

We report successful treatment of bacteremia caused by Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae in an immunocompromised patient using a novel antibiotic regimen that included oral fosfomycin. A 35-year-old man with history of mantle cell lymphoma was admitted to our tertiary care center after presenting with abdominal pain and low-grade temperatures 2 days following myeloablative autologous peripheral blood stem cell transplant. The patient developed septic shock despite initiation of broad-spectrum antibiotics, vancomycin, and piperacillin-tazobactam. Blood cultures grew multidrugresistant KPC-producing K pneumoniae, with only intermediate susceptibility to tetracycline, which was on national shortage at that time. Based on culture results and the available literature, various combinations of antibiotics, including meropenem, tigecycline, amikacin, and colistimethate, were initiated in attempts to achieve synergy and eradicate the infection, but repeat blood cultures remained positive, and the patient continued to worsen clinically. Two days after the addition of high-dose oral fosfomycin (9 g by mouth every 8 hours) in combination with intravenous (IV) doxycycline 100 mg twice daily and meropenem 1 g every 8 hours, blood cultures showed no growth. The patient was afebrile, alert, and clinically stable within 3 days of culture clearance. The final antibiotic regimen of IV doxycycline, meropenem, and high-dose oral fosfomycin continued for 2 weeks from the first negative culture. On completion of therapy, repeat cultures remained negative, all antibiotics were discontinued, and the patient was discharged home from the hospital. Other than causing clinically significant diarrhea, fosfomycin was well tolerated. Data are limited on effective antimicrobial treatment of infections caused by carbapenemase-producing K pneumoniae. Studies highlight the difficulty of eradicating KPC infections but suggest that combining antimicrobials may achieve synergy against KPC isolates. Fosfomycin has demonstrated activity against various KPC isolates, and European studies have shown successful treatment of highly resistant KPC infections with the addition of IV fosfomycin to antibiotic regimens. Because IV fosfomycin is not available in the United States, our team extrapolated an oral fosfomycin dose based on the dose of 3 g IV every 8 hours used by Sbrana et al. Taking into account the drug’s approximate 30% oral bioavailability, the patient received fosfomycin 9 g by mouth every 8 hours, with the aim of achieving adequate blood concentrations despite the inability to administer fosfomycin intravenously. Results of advanced microbiological synergy testing revealed that the KPC isolate was sensitive to meropenem and fosfomycin in combination but resistant to each drug alone, affirming our decision to add fosfomycin. The advanced synergy testing also revealed the combination of doxycycline and meropenem to be synergistic, whereas combinations including amikacin and colistimethate offered no benefit. It is impossible to pinpoint which agent or combination led to clearance of blood cultures. However, based on the timing of fosfomycin initiation and the subsequent eradication of infection, high-dose oral fosfomycin may have played a significant role in successfully treating this highly resistant KPC infection.

Doxycycline desensitization for a suspected case of ehrlichiosis.

Drug desensitization can achieve a temporary state of tolerance in individuals with histories of acute onset adverse reactions to specific medications. Desensitization can be effective for individuals with IgE-, IgG-, or other acute mechanism-mediated reactions. Tetracyclines have never been shown to induce antigen-specific IgE. Administration of doubling doses of the target medication during the desensitization process may cause mast cells and basophils involved in the allergic response to become hyporesponsive, thus inducing a state of temporary immune tolerance to the medication. Desensitization to

Efficacy and Outcomes After Vasopressin Guideline Implementation in Septic Shock

Background: In septic shock, the dose of norepinephrine (NE) at which vasopressin (AVP) should be added is unknown. Following an increase in AVP price, our medical intensive care unit (MICU) revised its vasopressor guidelines to reserve AVP for patients requiring greater than 50 µg/min of NE. Objective: The purpose of this study is to compare efficacy and safety outcomes for patients admitted before the guideline revision with those for patients admitted after the revision. Methods: This was a single-center, retrospective cohort study of patients admitted to Vanderbilt University Medical Center from November 1, 2014, to November 30, 2015. Before June 1, 2015, the vasopressor guidelines recommended initiation of AVP for patients requiring 10 µg/min of NE or greater. After June 1, 2015, the guidelines recommended initiation of AVP at a NE dose of 50 µg/min or greater. Results: Time to achieve goal mean arterial pressure (MAP) was shorter in the postintervention group (2.0 vs 1.3 hours; P = 0.03) in univariate analysis but not after adjusting for prespecified confounders. Incidence of new arrhythmias was similar between the 2 groups (14.9% vs 10.9%; P = 0.567). In multivariable analysis accounting for baseline severity of illness, admission after the revision was associated with decreased 28-day mortality (odds ratio = 0.34; 95% CI = 0.16-0.71; P = 0.004). Conclusions: Use of a vasopressor guideline restricting AVP initiation in septic patients to those on at least 50 µg/min of NE appeared to be safe and did not affect the time to reach goal MAP.

Linezolid Desensitization for a Patient with Multiple Medication Hypersensitivity Reactions

OBJECTIVE To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. CASE SUMMARY A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. DISCUSSION Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. CONCLUSIONS Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.