Management of Respiratory Failure in Hemorrhagic Shock.

Hemorrhagic shock results in acute respiratory failure due to respiratory muscle fatigue and inadequate pulmonary blood flow. Because positive pressure ventilation can reduce venous return and cardiac output, clinicians should use the minimum possible mean airway pressure during assisted or mechanical ventilation, particularly during episodes of severe hypovolemia. Hypoperfusion also worsens dead space fraction. Therefore, clinicians should monitor capnography during mechanical ventilation and recognize that hypercapnia may be treated with fluid resuscitation rather than increasing minute ventilation.

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia.

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following. METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6). RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following  was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

Timing is everything: Early do-not-resuscitate orders in the intensive care unit and patient outcomes.

BACKGROUND: The use of Do-Not-Resuscitate (DNR) orders has increased but many are placed late in the dying process. This study is to determine the association between the timing of DNR order placement in the intensive care unit (ICU) and nurses' perceptions of patients' distress and quality of death. METHODS: 200 ICU patients and the nurses (n = 83) who took care of them during their last week of life were enrolled from the medical ICU and cardiac care unit of New York Presbyterian Hospital/Weill Cornell Medicine in Manhattan and the surgical ICU at the Brigham and Women's Hospital in Boston. Nurses were interviewed about their perceptions of the patients' quality of death using validated measures. Patients were divided into 3 groups-no DNR, early DNR, late DNR placement during the patient's final ICU stay. Logistic regression analyses modeled perceived patient quality of life as a function of timing of DNR order placement. Patient's comorbidities, length of ICU stay, and procedures were also included in the model. RESULTS: 59 patients (29.5%) had a DNR placed within 48 hours of ICU admission (early DNR), 110 (55%) placed after 48 hours of ICU admission (late DNR), and 31 (15.5%) had no DNR order placed. Compared to patients without DNR orders, those with an early but not late DNR order placement had significantly fewer non-beneficial procedures and lower odds of being rated by nurses as not being at peace (Adjusted Odds Ratio namely AOR = 0.30; [CI = 0.09-0.94]), and experiencing worst possible death (AOR = 0.31; [CI = 0.1-0.94]) before controlling for procedures; and consistent significance in severe suffering (AOR = 0.34; [CI = 0.12-0.96]), and experiencing a severe loss of dignity (AOR = 0.33; [CI = 0.12-0.94]), controlling for non-beneficial procedures. CONCLUSIONS: Placement of DNR orders within the first 48 hours of the terminal ICU admission was associated with fewer non-beneficial procedures and less perceived suffering and loss of dignity, lower odds of being not at peace and of having the worst possible death.

Clinicians' Perceptions of Futile or Potentially Inappropriate Care and Associations with Avoidant Behaviors and Burnout.

Background: Futile or potentially inappropriate care (futile/PIC) for dying inpatients leads to negative outcomes for patients and clinicians. In the setting of rising end-of-life health care costs and increasing physician burnout, it is important to understand the causes of futile/PIC, how it impacts on care and relates to burnout. Objectives: Examine causes of futile/PIC, determine whether clinicians report compensatory or avoidant behaviors as a result of such care and assess whether these behaviors are associated with burnout. Design: Online, cross-sectional questionnaire. Setting/Subjects: Clinicians at two academic hospitals in New York City. Methods: Respondents were asked the frequency with which they observed or provided futile/PIC and whether they demonstrated compensatory or avoidant behaviors as a result. A validated screen was used to assess burnout. Measurements: Descriptive statistics, odds ratios, linear regressions. Results: Surveys were completed by 349 subjects. A majority of clinicians (91.3%) felt they had provided or "possibly" provided futile/PIC in the past six months. The most frequent reason cited for PIC (61.0%) was the insistence of the patient's family. Both witnessing and providing PIC were statistically significantly (p < 0.05) associated with compensatory and avoidant behaviors, but more strongly associated with avoidant behaviors. Provision of PIC increased the likelihood of avoiding the patient's loved ones by a factor of 2.40 (1.82-3.19), avoiding the patient by a factor of 1.83 (1.32-2.55), and avoiding colleagues by a factor of 2.56 (1.57-4.20) (all p < 0.001). Avoiding the patient's loved ones (ß = 0.55, SE = 0.12, p < 0.001), avoiding the patient (ß = 0.38, SE = 0.17; p = 0.03), and avoiding colleagues (ß = 0.78, SE = 0.28; p = 0.01) were significantly associated with burnout. Conclusions: Futile/PIC, provided or observed, is associated with avoidance of patients, families, and colleagues and those behaviors are associated with burnout.

Noninvasive ventilation: education and training. A narrative analysis and an international consensus document.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

Automated expiratory ventilation assistance through a small endotracheal tube can improve venous return and cardiac output.

BACKGROUND: Positive pressure ventilation can decrease venous return and cardiac output. It is not known if expiratory ventilation assistance (EVA) through a small endotracheal tube can improve venous return and cardiac output. RESULTS: In a porcine model, switching from conventional positive pressure ventilation to (EVA) with - 8 cmH20 expiratory pressure increased the venous return and cardiac output. The stroke volume increased by 27% when the subjects were switched from conventional ventilation to EVA [53.8 ± 7.7 (SD) vs. 68.1 ± 7.7 ml, p = 0.003]. After hemorrhage, subjects treated with EVA had higher median cardiac output, higher mean systemic arterial pressure, and lower central venous pressure at 40 and 60 min when compared with subjects treated with conventional ventilation with PEEP 0 cmH20. The median cardiac output was 41% higher in the EVA group than the control group at 60 min [2.70 vs. 1.59 L/min, p = 0.029]. CONCLUSION: EVA through a small endotracheal tube increased venous return, cardiac output, and mean arterial pressure compared with conventional positive pressure ventilation. The effects were most significant during hypovolemia from hemorrhage. EVA provided less effective ventilation than conventional positive pressure ventilation.

Association of Perceived Futile or Potentially Inappropriate Care With Burnout and Thoughts of Quitting Among Health-Care Providers.

BACKGROUND: Futile or potentially inappropriate care (futile/PIC) has been suggested as a factor contributing to clinician well-being; however, little is known about this association. OBJECTIVE: To determine whether futile/PIC provision is associated with measures of clinician well-being. DESIGN: Cross-sectional, self-administered, online questionnaire. SETTING: Two New York City Hospitals. PARTICIPANTS: Attending physicians, residents, nurses, and physician assistants in the fields of internal medicine, surgery, neurology, or intensive care. EXPOSURE(S): Provision of perceived futile/PIC. MEASUREMENTS: Main outcomes included (1) clinician burnout, measured using the Physician Worklife Study screen; (2) clinician depression, measured using the Patient Health Questionnaire; and (3) intention to quit, measured using questions assessing thoughts of quitting and how seriously it is being considered. RESULTS: Of 1784 clinicians who received surveys, 349 participated. Across all clinicians, 91% reported that they either had or had possibly provided futile/PIC to a patient. Overall, 43.4% of clinicians screened positive for burnout syndrome, 7.8% screened positive for depression, and 35.5% reported thoughts of leaving their job as a result of futile/PIC. The amount of perceived futile/PIC provided was associated with burnout (odds ratio [OR] 3.8 [16-30 patients vs 1-2 patients]; 95% confidence interval [CI]: 1.1-12.8) and having thoughts of quitting (OR, 7.4 [16-30 patients vs 1-2 patients]; 95% CI: 2.0-27), independent of depression, position, department, and the number of dying patients cared for. CONCLUSIONS: A large majority of clinicians report providing futile/PIC, and such care is associated with measures of clinician well-being, including burnout and intention to quit.

Underdetection and Undertreatment of Dyspnea in Critically Ill Patients.

Rationale: Dyspnea is a common and distressing physical symptom among patients in the ICU and may be underdetected and undertreated. Objectives: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment. Methods: This was an observational study of patients (n = 138) hospitalized in a medical ICU (MICU). Nurses and patients' personal caregivers at the bedside reported on their perception of patients' symptoms. Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate to severe dyspnea was similar or greater than that of pain (P < 0.05 for caregiver and nurse ratings). Personal caregivers' ratings of dyspnea had substantial agreement with patient ratings (κ = 0.65, P < 0.001), but nurses' ratings were not significantly related to patient ratings (κ = 0.19, P = 0.39). Nurse detection of moderate to severe pain was significantly associated with opioid treatment (odds ratio, 2.70; 95% confidence interval, 1.10-6.60; P = 0.03); however, nurse detection of moderate to severe dyspnea was not significantly associated with any assessed treatment. Conclusions: Dyspnea was reported at least as frequently as pain among the sampled MICU patients. Personal caregivers had good agreement with patient reports of moderate to severe dyspnea. However, even when detected by nurses, dyspnea appeared to be undertreated. These findings suggest the need for improved detection and treatment of dyspnea in the MICU.

Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials.

BACKGROUND: Observational studies suggest that some patients meeting criteria for ARDS no longer fulfill the oxygenation criterion early in the course of their illness. This subphenotype of rapidly improving ARDS has not been well characterized. We attempted to assess the prevalence, characteristics, and outcomes of rapidly improving ARDS and to identify which variables are useful to predict it. METHODS: A secondary analysis was performed of patient level data from six ARDS Network randomized controlled trials. We defined rapidly improving ARDS, contrasted with ARDS > 1 day, as extubation or a Pao2 to Fio2 ratio (Pao2:Fio2) > 300 on the first study day following enrollment. RESULTS: The prevalence of rapidly improving ARDS was 10.5% (458 of 4,361 patients) and increased over time. Of the 1,909 patients enrolled in the three most recently published trials, 197 (10.3%) were extubated on the first study day, and 265 (13.9%) in total had rapidly improving ARDS. Patients with rapidly improving ARDS had lower baseline severity of illness and lower 60-day mortality (10.2% vs 26.3%; P < .0001) than ARDS > 1 day. Pao2:Fio2 at screening, change in Pao2:Fio2 from screening to enrollment, use of vasopressor agents, Fio2 at enrollment, and serum bilirubin levels were useful predictive variables. CONCLUSIONS: Rapidly improving ARDS, mostly defined by early extubation, is an increasingly prevalent and distinct subphenotype, associated with better outcomes than ARDS > 1 day. Enrollment of patients with rapidly improving ARDS may negatively affect the prognostic enrichment and contribute to the failure of therapeutic trials.

A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS. METHODS: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes. RESULTS: No participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects. CONCLUSION: Precise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02425579. FUNDING: NIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.

Investigational use of PEGylated carboxyhemoglobin bovine in a Jehovah's Witness with hemorrhagic shock.

BACKGROUND: Jehovah's Witnesses pose a clinical challenge in the setting of critical anemia. Most do not accept transfusions, but some accept hemoglobin-based oxygen carriers on a compassionate-use basis. PEGylated carboxyhemoglobin bovine (PCHB) is an acellular dual-action carbon monoxide (CO)-releasing and oxygen transfer agent currently being investigated in Phase II clinical trials. CASE REPORT: We present the case of a 42-year-old Jehovah's Witness with an acute upper gastrointestinal bleed and hemorrhagic shock who required emergent PCHB for stabilization during lifesaving interventions. After PCHB infusion, the patient's shock and encephalopathy improved with decreased vasopressor requirement. Through gastroenterology and interventional radiology procedures, the patient's bleeding stabilized. While receiving five additional doses of PCHB and other supportive therapies (iron, folate, vitamin B12, darbepoetin alfa), the patient was extubated and weaned off vasopressors. CONCLUSIONS: PCHB was used to stabilize (bridge) a critically ill anemic patient for lifesaving interventions without adverse effects. Additional studies are warranted to explore the drug's safety profile and efficacy in patients declining blood products.

Dying Patient and Family Contributions to Nurse Distress in the ICU.

RATIONALE: Caring for patients at the end of life is emotionally taxing and may contribute to burnout. Nevertheless, little is known about the factors associated with emotional distress in intensive care unit (ICU) nurses. OBJECTIVES: To identify patient and family factors associated with nurses' emotional distress in caring for dying patients in the ICU. METHODS: One hundred nurses who cared for 200 deceased ICU patients at two large academic medical centers in the Northeast United States were interviewed about patients' psychological and physical symptoms, their reactions to those patient experiences (e.g., emotional distress), and perceived factors contributing to their emotional distress. Logistic regression analyses modeled nurses' emotional distress as a function of patient symptoms and care. RESULTS: Patients' overall quality of death (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.31-7.25), suffering (OR, 2.34; CI, 1.03-5.29), and loss of dignity (OR, 2.95; CI, 1.19-7.29) were significantly associated with nurse emotional distress. Some 40.5% (79 of 195) of nurses identified families' fears of patient death, and 34.4% (67 of 195) identified families' unrealistic expectations as contributing to their own emotional distress. CONCLUSIONS: Patients' emotional distress, physical distress, and perceived quality of death are associated with nurse emotional distress. Unrealistic family expectations for the patient may be a source of nurse emotional distress. Improving patients' quality of death, including enhancing their dignity, reducing their suffering, and promoting acceptance of an impending death among family members may improve the emotional health of nurses.

Pulmonary effects of aging.

PURPOSE OF REVIEW: As the population ages, the increase in chronic illnesses among patients with decreasing lung function will pose a major public health challenge. Determining which elderly patients are fit for surgery is an increasingly important skill. Anesthetic care of elderly patients requires an understanding of the effects that chronic diseases have on normal age-related changes in physiology and function. Postoperative respiratory complications are significantly increased in patients over 65 years of age, especially those with preexisting diseases. RECENT FINDINGS: Advanced age is associated with changes in the immunity of the pulmonary system. Dysregulation of pro-inflammatory mediators and antimicrobial defense systems contribute to a reduction in pulmonary function and its response to infections. Aging is also associated with a disruption of the function of alveolar macrophages, neutrophils, and natural killer cells. SUMMARY: Aging can increase the risk of postoperative complications because of a loss of physiologic reserve and airway defenses. These limitations may only become apparent after the stressors of surgery and anesthesia.

Annexin A2 supports pulmonary microvascular integrity by linking vascular endothelial cadherin and protein tyrosine phosphatases.

Relative or absolute hypoxia activates signaling pathways that alter gene expression and stabilize the pulmonary microvasculature. Alveolar hypoxia occurs in disorders ranging from altitude sickness to airway obstruction, apnea, and atelectasis. Here, we report that the phospholipid-binding protein, annexin A2 (ANXA2) functions to maintain vascular integrity in the face of alveolar hypoxia. We demonstrate that microvascular endothelial cells (ECs) from Anxa2-/- mice display reduced barrier function and excessive Src-related tyrosine phosphorylation of the adherens junction protein vascular endothelial cadherin (VEC). Moreover, unlike Anxa2+/+ controls, Anxa2-/- mice develop pulmonary edema and neutrophil infiltration in the lung parenchyma in response to subacute alveolar hypoxia. Mice deficient in the ANXA2-binding partner, S100A10, failed to demonstrate hypoxia-induced pulmonary edema under the same conditions. Further analyses reveal that ANXA2 forms a complex with VEC and its phosphatases, EC-specific protein tyrosine phosphatase (VE-PTP) and Src homology phosphatase 2 (SHP2), both of which are implicated in vascular integrity. In the absence of ANXA2, VEC is hyperphosphorylated at tyrosine 731 in response to vascular endothelial growth factor, which likely contributes to hypoxia-induced extravasation of fluid and leukocytes. We conclude that ANXA2 contributes to pulmonary microvascular integrity by enabling VEC-related phosphatase activity, thereby preventing vascular leak during alveolar hypoxia.