Tufik R. Assad

Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill

RATIONALE Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia. OBJECTIVES To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit. METHODS This was a randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after completion of endotracheal intubation. MEASUREMENTS AND MAIN RESULTS Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% confidence interval for the difference, -1.6 to 7.4%; P = 0.16). There was no difference between apneic oxygenation and usual care in incidence of oxygen saturation less than 90% (44.7 vs. 47.2%; P = 0.87), oxygen saturation less than 80% (15.8 vs. 25.0%; P = 0.22), or decrease in oxygen saturation greater than 3% (53.9 vs. 55.6%; P = 0.87). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality were similar between study groups. CONCLUSIONS Apneic oxygenation does not seem to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared with usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults. Clinical trial registered with www.clinicaltrials.gov (NCT 02051816).

Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults.

Objective:To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults. Design:A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows. Setting:Medical ICU in a tertiary, academic medical center. Patients:Critically ill patients 18 years old or older. Interventions:Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation. Measurements and Main Results:Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator’s previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82–5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy. Conclusions:In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications.

Hemodynamic Evidence of Vascular Remodeling in Combined Post- and Precapillary Pulmonary Hypertension

Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH.

A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults

BACKGROUND: Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. METHODS: Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack‐Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. RESULTS: The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%‐99%) with the ramped position vs 92% (IQR, 79%‐98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. CONCLUSIONS: In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov

Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension

Importance Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH. Objective To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH. Design, Setting, and Participants Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively. Exposures Mean pulmonary arterial pressure. Main Outcome and Measures Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis. Results We identified 4343 patients (mean [SD] age, 59 [15] years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with borderline PH who underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase in mPAP of 5 mm Hg (interquartile range, −1 to 11 mm Hg; P < .001). Conclusions and Relevance Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.

Metabolic Dysfunction in Pulmonary Arterial Hypertension

Previously considered a disease isolated to the pulmonary circulation, pulmonary arterial hypertension is now being recognized as a systemic disorder that is associated with significant metabolic dysfunction. Numerous animal models have demonstrated the development of pulmonary arterial hypertension following the onset of insulin resistance, indicating that insulin resistance may be causal. Recent publications highlighting alterations in aerobic glycolysis, fatty acid oxidation, and the tricarboxylic acid cycle in the pulmonary circulation and right ventricle have expanded our understanding of the complex pathobiology of this disease. By targeting these derangements in metabolism, numerous researchers are investigating noninvasive techniques to monitor disease activity and therapeutics that address the underlying metabolic condition. In the following review, we will explore pre-clinical and clinical studies investigating the metabolic dysfunction seen in pulmonary arterial hypertension.

Thermodilution vs Estimated Fick Cardiac Output Measurement in Clinical Practice: An Analysis of Mortality From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and Vanderbilt University

Importance Thermodilution (Td) and estimated oxygen uptake Fick (eFick) methods are widely used to measure cardiac output (CO). They are often used interchangeably to make critical clinical decisions, yet few studies have compared these approaches as applied in medical practice. Objectives To assess agreement between Td and eFick CO and to compare how well these methods predict mortality. Design, Setting, and Participants This investigation was a retrospective cohort study with up to 1 year of follow-up. The study used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) program. The findings were corroborated in a cohort of patients cared for at Vanderbilt University, an academic referral center. Participants were more than 15 000 adults who underwent right heart catheterization, including 12 232 in the Veterans Affairs cohort between October 1, 2007, and September 30, 2013, and 3391 in the Vanderbilt cohort between January 1, 1998, and December 31, 2014. Exposures A single cardiac catheterization was performed on each patient with CO estimated by both Td and eFick methods. Cardiac output was indexed to body surface area (cardiac index [CI]) for all analyses. Main Outcomes and Measures All-cause mortality over 90 days and 1 year after catheterization. Results Among 12 232 VA patients (mean [SD] age, 66.4 [9.9] years; 3.3% female) who underwent right heart catheterization in this cohort study, Td and eFick CI estimates correlated modestly (r = 0.65). There was minimal mean difference (eFick minus Td = −0.02 L/min/m2, or −0.4%) but wide 95% limits of agreement between methods (−1.3 to 1.3 L/min/m2, or −50.1% to 49.4%). Estimates differed by greater than 20% for 38.1% of patients. Low Td CI (<2.2 L/min/m2 compared with normal CI of 2.2-4.0 L/min/m2) more strongly predicted mortality than low eFick CI at 90 days (Td hazard ratio [HR], 1.71; 95% CI, 1.47-1.99; &khgr;2 = 49.5 vs eFick HR, 1.42; 95% CI, 1.22-1.64; &khgr;2 = 20.7) and 1 year (Td HR, 1.53; 95% CI, 1.39-1.69; &khgr;2 = 71.5 vs eFick HR, 1.35; 1.22-1.49; &khgr;2 = 35.2). Patients with a normal CI by both methods had 12.3% 1-year mortality. There was no significant additional risk for patients with a normal Td CI but a low eFick CI (12.9%, P = .51), whereas a low Td CI but normal eFick CI was associated with higher mortality (15.4%, P = .001). The results from the Vanderbilt cohort were similar in the context of a more balanced sex distribution (46.6% female). Conclusions and Relevance There is only modest agreement between Td and eFick CI estimates. Thermodilution CI better predicts mortality and should be favored over eFick in clinical practice.

A Multicenter Randomized Trial of a Checklist for Endotracheal Intubation of Critically Ill Adults

BACKGROUND: Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation. METHODS: A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation. RESULTS: The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79‐98) in the checklist group vs 93% (IQR, 84‐100) with usual care (P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94‐133) in the checklist group vs 108 mm Hg (IQR, 90‐132) in the usual care group (P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life‐threatening procedural complications (40.8% vs 32.6%; P = .20). CONCLUSIONS: The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

PULMONARY HYPERTENSION AND CHRONIC KIDNEY DISEASE: INVASIVE HEMODYNAMIC ETIOLOGY AND OUTCOMES IN A LARGE ELECTRONIC MEDICAL RECORD-BASED COHORT

Pulmonary hypertension (PH) is common in chronic kidney disease (CKD), but the hemodynamic etiology (precapillary vs. post capillary) and outcomes across CKD stages have not been well characterized. We extracted clinical and hemodynamic data from our de-identified electronic medical record in all

Pulmonary hypertension in patients with chronic kidney disease: invasive hemodynamic etiology and outcomes

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) and associated with increased mortality but the hemodynamic profiles, clinical risk factors, and outcomes have not been well characterized. Our objective was to define the hemodynamic profile and related risk factors for PH in CKD patients. We extracted clinical and hemodynamic data from Vanderbilt’s de-identified electronic medical record on all patients undergoing right heart catheterization during 1998–2014. CKD (stages III–V) was defined by estimated glomerular filtration rate thresholds. PH was defined as mean pulmonary pressure ≥ 25 mmHg and categorized into pre-capillary and post-capillary according to consensus recommendations. In total, 4635 patients underwent catheterization: 1873 (40%) had CKD; 1518 (33%) stage 3, 230 (5%) stage 4, and 125 (3%) stage 5. PH was present in 1267 (68%) of these patients. Post-capillary (n = 965, 76%) was the predominant PH phenotype among CKD patients versus 302 (24%) for pre-capillary (P < 0.001). CKD was independently associated with pulmonary hypertension (odds ratio = 1.4, 95% confidence interval = 1.18–1.65). Mortality among CKD patients rose with worsening stage and was significantly increased by PH status. PH is common and independently associated with mortality among CKD patients referred for right heart catheterization. Post-capillary was the most common etiology of PH. These data suggest that PH is an important prognostic co-morbidity among CKD patients and that CKD itself may have a role in the development of pulmonary vascular disease in some patients.