Society of Critical Care Medicine Clinical Practice Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.

Therapeutic review: The role of tranexamic acid in management of traumatic brain injury, nontraumatic intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage.

PURPOSE: To summarize current literature evaluating tranexamic acid in the management of intracranial bleeding associated with traumatic and nontraumatic brain injuries and implications for clinical practice. SUMMARY: Intracranial hemorrhage, regardless of etiology, is associated with high morbidity and mortality. Tranexamic acid is an antifibrinolytic with anti-inflammatory properties shown to reduce mortality in trauma patients with extracranial injuries. In traumatic brain injury, a large randomized trial found no difference in outcomes when tranexamic acid was compared to placebo; however, subgroup analyses suggested that it may reduce head injury-related mortality in the context of mild-to-moderate injury if treatment occurs within 1 hour of symptom onset. More recent out-of-hospital data have disputed these findings and even suggested harm in severely injured patients. In spontaneous, nontraumatic intracranial hemorrhage, treatment with tranexamic acid did not result in a difference in functional status; however, rates of hematoma expansion, even though modest, were significantly reduced. In aneurysmal subarachnoid hemorrhage, tranexamic acid may prevent rebleeding, but has not led to improved outcomes or reduced mortality, and there is concern for increased incidence of delayed cerebral ischemia. Overall, tranexamic acid has not been shown to result in increased risk of thromboembolic complications across these classes of brain injury. CONCLUSION: Despite its favorable safety profile overall, tranexamic acid does not seem to improve functional outcomes and cannot be routinely recommended. More data are needed to determine which head injury subpopulations are most likely to benefit from tranexamic acid and which patients are at increased risk for harm.

An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers.

BACKGROUND: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. RESEARCH QUESTION: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? STUDY DESIGN AND METHODS: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. RESULTS: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. INTERPRETATION: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics.

Pharmacists as members of an interdisciplinary pulmonary embolism response team.

Introduction: Pulmonary embolism response teams (PERTs) were developed to assist with diagnosis, risk stratification, and management of intermediate and high-risk pulmonary embolism (PE) and have been shown to reduce 90-day mortality. The pharmacist's role on the PERT is not well defined. Objectives: Describe the pharmacist's role as a PERT member and determine if pharmacists can improve time to anticoagulation and promote use of low molecular weight heparin (LMWH) instead of unfractionated heparin (UFH). Methods: A retrospective, observational study of adult patients with massive or submassive PE between January 2014 and May 2020. Patient demographics, clinical variables, anticoagulation treatment/timing, and pharmacist activities during PERT response were evaluated. Patients were divided into three groups for comparisons (pre-PERT vs post-PERT with a pharmacist vs post-PERT without a pharmacist). Wilcoxon rank-sum or Kruskal-Wallis test and chi-squared analysis were used for continuous and categorical data, respectively. Results: A total of 573 patients were included (mean age 63.2 ± 15.6 years, 54% male, 78% submassive PE); 137 in the pre-PERT and 436 in the post-PERT groups. Within the post-PERT group, 305 patients (70%) had a pharmacist as a member of the PERT, of which 222 (73%) had a documented pharmacotherapy-related intervention/activity. Most (n = 178, 58%) involved a pharmacist facilitating ordering/administration of an anticoagulant/thrombolytic. Median time from diagnosis to anticoagulation was significantly reduced in the post-PERT groups (pre-PERT: 104 minutes [IQR 124.5], post-PERT with a pharmacist: 63 minutes [IQR 84], post-PERT without a pharmacist: 75.5 minutes [IQR 113], P = .0001). More patients in the post-PERT groups received LMWH compared to UFH when a pharmacist was involved vs without a pharmacist (69.5% vs 53.3%, P = .0019) and major bleeding events were reduced (pre-PERT: 14.6%, post-PERT with a pharmacist: 4.6%, and post-PERT without a pharmacist: 9.9%, P = .0013). Conclusion: Pharmacists have an active role on the PERT and their involvement was associated with a shorter diagnosis to anticoagulation time, increased LMWH use, and fewer major bleeding events.

Multicenter Retrospective Review of Ketamine Use in the ICU.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study. CONCLUSIONS AND RELEVANCE: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.

A Retrospective Characterization of Dexmedetomidine-Suspected Fever and Its Consequences in Adult Critically Ill Patients.

BACKGROUND: Current evidence for dexmedetomidine-suspected fever (DSF) is limited. Lack of recognition may lead to costly or potentially harmful interventions for critically ill patients. OBJECTIVE: The primary objective was to characterize escalations of care related to DSF. Secondary objectives were to describe the incidence, severity, and consequences associated with DSF. METHODS: A retrospective review was conducted in critically ill adults who developed fever ≥39°C within 12 h from initiation of dexmedetomidine, with resolution of fever to <39°C within 12 h after discontinuation. The primary outcome was percentage of patients who received an escalation of care due to fever. Secondary outcomes included the percentage of patients who developed a multidrug-resistant organism or Clostridium difficile infection. RESULTS: Eighteen of 3943 patients screened in 4099 encounters met criteria for DSF (0.4%). The majority were white (83.3%), male (66.7%), and underwent cardiac surgery (61.1%). Median (interquartile range [IQR]) time to fever onset and resolution were 5.5 (3.6-7.6) and 1.3 (1.0-2.9) h. Nine patients (50%) underwent infectious workup including antimicrobial initiation (n = 1, 5.6%), broadening of antimicrobials (n = 4, 22.2%), or culture collection (n = 9, 50%). Eleven patients (61.1%) underwent attempted temperature reduction. Twelve patients (66.7%) underwent diagnostic imaging. Incidence of multidrug-resistant organism and C. difficile infection were low (11.1 and 16.7% of fever patients, respectively). CONCLUSION AND RELEVANCE: Incidence of DSF was low and more common in cardiac surgery patients. Unrecognized DSF led to an escalation of care in most patients. Dexmedetomidine exposure should be considered as a potential cause of fever in critically ill adults.

Polypharmacy prior to in-hospital cardiac arrest among patients with cardiopulmonary diseases: A pilot study.

BACKGROUND: Patterns of medication administration prior to in-hospital cardiac arrest (I-HCA) and the potential impact of these on patient outcomes is not well-established. Accordingly, types of medications administered in the 72 h prior to I-HCA were examined in relation to initial rhythms of I-HCA and survival. METHODS: A retrospective, pilot study was conducted among 96 patients who experienced I-HCA. Clinical characteristics and treatments including medications were extracted from electronic health records. Relative risk (RR) of medications or class of medications associated with the initial rhythms of I-HCA and return of spontaneous circulation (ROSC) were calculated. RESULTS: Two distinct sub-groups were identified that did not survive to hospital discharge (n = 31): 1) those who received either vasopressin/desmopressin (n = 16) and 2) those who received combinations of psychotherapeutic agents with anxiolytics, sedatives, and hypnotics (n = 15) prior to I-HCA. The risk of pulseless electrical activity and asystolic arrest was high in patients who received sympathomimetic agents alone or in combination with ß-Adrenergic blocking agents, (RR = 1.40, 1.41, respectively). Vasopressin and a combination of vasopressin and fentanyl were associated with risk of unsuccessful ROSC (RR = 2.50, 2.38, respectively). CONCLUSIONS: The types of medications administered during inpatient care may serve as a surrogate marker for identifying patients at risk of specific initial rhythms of I-HCA and survival.

The impact of a pulmonary embolism response team on the efficiency of patient care in the emergency department.

The concept of a pulmonary embolism response team (PERT) is multidisciplinary, with the hope that it may positively impact patient care, hospital efficiency, and outcomes in the treatment of patients with intermediate and high risk pulmonary embolism (PE). Clinical characteristics of a baseline population of patients presenting with submassive and massive PE to URMC between 2014 and 2016 were examined (n = 159). We compared this baseline population before implementation of a PERT to a similar population of patients at 3-month periods, and then as a group at 18 months after PERT implementation (n = 146). Outcomes include management strategies and efficiency of the emergency department (ED) in diagnosing, treating, and dispositioning patients. Before PERT, patients with submassive and massive PE were managed fairly conservatively: heparin alone (85%), or additional advanced therapies (15%). Following PERT, submassive and massive PE were managed as follows: heparin alone (68%), or additional advanced therapies (32%). Efficiency of the ED in managing high risk PE significantly improved after PERT compared with before PERT; where triage to diagnosis time was reduced (384 vs. 212 min, 45% decrease, p = 0.0001), diagnosis to heparin time was reduced (182 vs. 76 min, 58% decrease, p = 0.0001), and the time from triage to disposition was reduced (392 vs. 290 min, 26% decrease, p < 0.0001). Our analysis showed that following PERT implementation, patients with intermediate and high risk acute PE received more aggressive and advanced treatment modalities and received significantly expedited care in the ED.

Current practices and safety of medication use during rapid sequence intubation.

PURPOSE: Characterize medication practices during and immediately after rapid sequence intubation (RSI) by provider/location and evaluate adverse drug events. MATERIALS AND METHODS: This was a multicenter, observational, cross-sectional study of adult and pediatric intensive care unit and emergency department patients over a 24-h period surrounding first intubation. RESULTS: A total of 404 patients from 34 geographically diverse institutions were included (mean age 58 ±â€¯22 years, males 59%, pediatric 8%). During RSI, 21%, 87%, and 77% received pre-induction, induction, and paralysis, respectively. Significant differences in medication use by provider type were seen. Etomidate was administered to 58% with sepsis, but was not associated with adrenal insufficiency. Ketamine was associated with hypotension post-RSI [RR = 1.78 (1.36-2.35)] and use was low with traumatic brain injury/stroke (1.5%). Succinylcholine was given to 67% of patients with baseline bradycardia and was significantly associated with bradycardia post-RSI [RR = 1.81 (1.11-2.94)]. An additional 13% given succinylcholine had contraindications. Sedation practices post-RSI were not consistent with current practice guidelines and most receiving a non-depolarizing paralytic did not receive adequate sedation post-RSI. CONCLUSIONS: Medication practices during RSI vary amongst provider and medications are often used inappropriately. There is opportunity for optimization of medication use during RSI.

The Use of Continuous Ketamine for Analgesia and Sedation in Critically Ill Patients with Opioid Abuse: A Case Series.

Managing pain and agitation in patients with opioid abuse is becoming more common in intensive care units. Tolerance to commonly used agents is often observed, leading to inadequate pain control and increased agitation. Ketamine's unique mechanism of action and opioid-sparing effects make it an ideal agent for patients with suboptimal response to opioid therapy. This report describes our experience using continuous ketamine infusions for analgesia and sedation in four mechanically ventilated patients with histories of opioid abuse that had suboptimal response to standard therapy. Ketamine was successful in improving analgesia and sedation in three patients while reducing the need for other analgesics and sedatives with minimal adverse effects. Continuous ketamine infusions may be useful to facilitate mechanical ventilation in patients with histories of opioid abuse with minimal toxicity. More information is needed on the optimal dose and titration parameters.

Pharmacists as Members of the Rapid Response Team.

PURPOSE: Rapid response teams (RRTs) have been developed to provide early therapy to patients with risk factors for cardiopulmonary arrest. We sought to investigate the role a pharmacist could have as a member of the RRT. METHODS: Two pharmacists trained in critical care and emergency medicine proposed a pilot program to determine whether a pharmacist as a member of the RRT could help to optimize pharmacotherapy and facilitate medication administration. During response, 1 pharmacist was at the bedside with the RRT for patient evaluation, consult, chart review, and to facilitate medication administration. The responding RRT pharmacist collected patient demographics, medications administered, pharmacotherapy recommendations, and time commitment. RESULTS: The pharmacists responded to 32 RRT alerts. A majority (65.6%) of patients required at least 1 medication, and a total of 45 medications were administered. The pharmacists performed 49 pharmacotherapy-related interventions in 21 patients. These included medication facilitation (15), dose (15) or therapy (8) recommendations, and adding (6) or discontinuing (5) a medication. The pharmacists spent a median time of 15 minutes (interquartile range [IQR] 15, range 2-70) for each RRT alert and a total of 612 minutes (10.2 hours). CONCLUSION: With a minimal time commitment, pharmacists can be valuable members of the RRT.

Mortality following rasburicase-induced methemoglobinemia.

OBJECTIVE: To report a case of mortality following rasburicase-induced methemoglobinemia. CASE SUMMARY: A 62-year-old African American male with chronic lymphocytic leukemia and small lymphocytic lymphoma was admitted for tumor lysis syndrome and renal failure. He was treated with 2 doses of rasburicase, subsequently developed methemoglobinemia, and required intubation, multiple packed red blood cell (PRBC) transfusions, and 2 doses of methylene blue. A screen for glucose-6 phosphate dehydrogenase (G6PD) deficiency was negative. His course was complicated by hemolytic anemia, nosocomial pneumonia, Clostridium difficile infection, and septic shock. His methemoglobin concentrations normalized over several days; however, the patient eventually died on hospital day 16. An objective causality assessment revealed that the adverse drug reaction was probable. DISCUSSION: Our case was similar to previously published cases, except that our patient died and his G6PD screen was negative. Although it was negative, it is likely that this was a false negative result because this blood was drawn shortly after PRBC transfusions and during active hemolysis. Both these are likely to cause false-negative results. CONCLUSIONS: Methemoglobinemia is a rare adverse effect associated with the use of rasburicase and occurs most often in patients with G6PD deficiency. G6PD testing should not be ordered during active hemolysis or after blood transfusion because this may lead to false-negative results. Methylene blue should not be used as an antidote because it may worsen hemolytic anemia in patients with G6PD deficiency.

Octreotide for the treatment of hypoglycemia after insulin glargine overdose.

BACKGROUND: Intentional insulin glargine overdose is rarely reported in the literature, but usually results in prolonged hypoglycemia requiring intensive care unit admission. OBJECTIVE: We report a case of using octreotide to treat prolonged hypoglycemia after a large insulin glargine overdose. CASE REPORT: A 56-year-old man with type 2 diabetes mellitus presented to the Emergency Department after a multidrug overdose including up to 3,300 units insulin glargine. He required admission to the intensive care unit for mechanical ventilation and blood-glucose monitoring every 30 to 60 min. He received a continuous dextrose infusion for >100 h for persistent hypoglycemia. Octreotide, a somatostatin analogue, was given on day 4 of admission in an attempt to inhibit any insulin secretion from the pancreas that might be occurring in response to the dextrose infusion and to minimize the amount of fluid being given. After three doses, improvements in the patient's blood glucoses were seen, however, this could have coincided with complete absorption of the insulin. CONCLUSIONS: Prolonged hypoglycemia often occurs after large overdoses of insulin glargine due to a depot effect at the site of injection. Octreotide is a potential adjunctive treatment to dextrose in patients with a functioning pancreas.