Sepsis and the Obesity Paradox: Size Matters in More Than One Way.

OBJECTIVES: Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Five community-based and one academic medical center in the Omaha, NE. PATIENTS: 7,967 adults hospitalized with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate. CONCLUSIONS: Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Atypical Guillain-Barré syndrome presenting with fluctuating weakness.

Guillain-Barré Syndrome (GBS) is an immune-mediated polyneuropathy, most often occurring within weeks of an infection. Cases of COVID-19-related GBS have been reported, and the typical presentation is a progressive ascending paralysis. We describe a case of a 40-year-old with recent symptomatic COVID-19 who presented with atypical GBS findings, hand weakness that progressed to tetraplegia within 24 hours. He had hyperreflexia on his initial exam and did not meet diagnostic criteria for GBS. Inconsistent neurological findings with spontaneous improvement of symptoms, unremarkable initial evaluation including lumbar puncture, and anxiety further complicated the diagnosis. On day 6, he was intubated for diaphragmatic paralysis, and repeat lumbar puncture showed albumin-cytologic dissociation. Intravenous immunoglobulin followed by plasmapheresis improved strength and allowed for extubation. This case highlights the difficulty of recognizing heterogenic GBS presentations.

A Retrospective Analysis of the Effects of Time on Compliance and Driving Pressures in ARDS.

BACKGROUND: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. METHODS: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment. RESULTS: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment (P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure. CONCLUSIONS: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

A case report of ceftriaxone-induced cardiopulmonary arrest.

Introduction: and Importance: Ceftriaxone is used frequently in treating infectious diseases. While hypersensitivity skin reactions are common with the use of ceftriaxone, anaphylactic reactions are rare. Case presentation: A 66-year-old female presented to our hospital with complaints of headache and sinus congestion. Vital signs showed hypoxia, and the physical exam was unremarkable. A computed tomography scan of the chest revealed right upper lobe pneumonia, and the patient was started on ceftriaxone and azithromycin. The patient went into asystole 1 min after ceftriaxone administration. She did not require cardiopulmonary resuscitative measures as she spontaneously transitioned to normal sinus rhythm. Given the timing of the event immediately after ceftriaxone administration, we determined ceftriaxone was the likely culprit. The patient received alternative treatment for pneumonia and recovered without sequelae. We added ceftriaxone to her allergy list. Clinical discussion: This case report highlights a rare adverse event associated with ceftriaxone. After an extensive literature search, we found only four other reported cases of cardiopulmonary arrest following ceftriaxone. The exact mechanism for this adverse event has not been fully elucidated. Conclusion: Clinicians should be aware of the potential for ceftriaxone-induced asystole, perform allergy reviews and obtain informed consent before its administration.

Prolonged Prehospital Time Is a Risk Factor for Pneumonia in Trauma (the PRE-TRIP Study): A Retrospective Analysis of the United States National Trauma Data Bank.

BACKGROUND: Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown. RESEARCH QUESTION: Is prolonged prehospital time an independent risk factor for pneumonia? STUDY DESIGN AND METHODS: We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016. RESULTS: Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P < .001). This association was primarily driven by patients with low Glasgow Coma Scale scores. Post-trauma pneumonia was uncommon (1.5% incidence) but was associated with a significant increase in mortality (P < .001, 4.3% mortality without pneumonia vs 12.1% mortality with pneumonia). Other pneumonia risk factors included age, sex, race, primary payor, trauma center teaching status, bed size, geographic region, intoxication, comorbid lung disease, steroid use, lower Glasgow Coma Scale score, higher Injury Severity Scale score, blood product transfusion, chest trauma, and respiratory burns. INTERPRETATION: Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making.

Multisystem inflammatory syndrome in adults: A rare sequela of SARS-CoV-2 infection.

Multisystem inflammatory syndrome in adults (MIS-A) came to attention back in June 2020, when the United States Center for Disease Control and Prevention (CDC) received initial reports regarding patients who had presented delayed and multisystem involvement of the disease, with clinical course resembling multisystem inflammatory syndrome in children (MIS-C). This study introduces a case of MIS-A, where the patient presented 3 weeks after initial COVID-19 exposure. His clinical course was consistent with the working definition of MIS-A as specified by the CDC. Aggressive supportive care in the intensive care unit, utilization of advanced heart failure devices, and immunomodulatory therapeutics (high-dose steroids, anakinra, intravenous immunoglobulin) led to clinical recovery. Management of MIS-A is a topic of ongoing research and needs more studies to elaborate on treatment modalities and clinical predictors.

Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies.

BACKGROUND: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. METHODS: Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. RESULTS: MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. CONCLUSIONS: In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Sepsis, the Administration of IV Fluids, and Respiratory Failure: A Retrospective Analysis-SAIFR Study.

BACKGROUND: Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking. RESEARCH QUESTION: Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg? STUDY DESIGN AND METHODS: This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD). RESULTS: A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups. INTERPRETATION: In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure.

The POSITIONED Study: Prone Positioning in Nonventilated Coronavirus Disease 2019 Patients-A Retrospective Analysis.

Given perceived similarities between coronavirus disease 2019 pneumonia and the acute respiratory distress syndrome, we explored whether awake self-proning improved outcomes in coronavirus disease 2019-infected patients treated in a rural medical center with limited resources during a significant local coronavirus disease 2019 outbreak. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Single-center rural community-based medical center in Grand Island, NE. PATIENTS: One hundred five nonintubated, coronavirus disease-infected patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After patients were educated on the benefits of awake self-proning, compliance was voluntary. The primary outcome was need for intubation during the hospital stay; secondary outcomes included serial peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios, in-hospital mortality, and discharge disposition. Of 105 nonintubated, coronavirus disease-infected patients, 40 tolerated awake self-proning. Patients who were able to prone were younger and had lower disease severity. The risk of intubation was lower in proned patients after adjusting for disease severity using Sequential Organ Failure Assessment scores (adjusted hazard ratio, 0.30; 95% CI, 0.09-0.96; p = 0.043) or Acute Physiology and Chronic Health Evaluation II scores (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.91; p = 0.034). No prone patient died compared with 24.6% of patients who were not prone (p < 0.001; number needed to treat = 5; 95% CI, 3-8). The probability of being discharged alive and peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios were statistically similar for both groups. CONCLUSIONS: Awake self-proning was associated with lower mortality and intubation rates in coronavirus disease 2019-infected patients. Prone positioning appears to be a safe and inexpensive strategy to improve outcomes and spare limited resources. Prospective efforts are needed to better delineate the effect of awake proning on oxygenation and to improve patients' ability to tolerate this intervention.