Persistence of live virus in critically ill patients infected with SARS-COV-2: a prospective observational study.

BACKGROUND: Research on the duration of infectivity of ICU patients with COVID-19 has been sparse. Tests based on Reverse Transcriptase polymerase chain reaction (RT-PCR) detect both live virus and non-infectious viral RNA. We aimed to determine the duration of infectiousness based on viral culture of nasopharyngeal samples of patients with COVID-19. METHODS: Prospective observational study in adult intensive care units with a diagnosis of COVID-19 Pneumonia. Patients had repeated nasopharyngeal sampling performed after day 10 of ICU admission. Culture positive rate (based on viral culture on Vero cells in a level 4 lab) and Cycle threshold from RT-PCR were measured. RESULTS: Nine patients of the 108 samples (8.3%, 95% CI 3.9-15.2%) grew live virus at a median of 13 days (interquartile range 11-19) after their initial positive test. 74.1% of patients were RT-PCR positive but culture negative, and the remaining (17.6%) were RT-PCR and culture negative. Cycle threshold showed excellent ability to predict the presence of live virus, with a Ct < 25 with an AUC of 0.90 (95% CI 0.83-0.97, p < 0.001). The specificity of a Ct > 25 to predict negative viral culture was 100% (95% CI 70-100%). CONCLUSION: 8.3% of our ICU patients with COVID-19 grew live virus at a median of 13 days post-initial positive RT-PCR test. Severity of illness, use of mechanical ventilation, and time between tests did not predict the presence of live virus. Cycle threshold of > 25 had the best ability to determine the lack of live virus in these patents.

A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair.

INTRODUCTION: Goal-directed therapy (GDT) has been shown in numerous studies to decrease perioperative morbidity and mortality. The mechanism of benefit of GDT, however, has not been clearly elucidated. Targeted resuscitation of the vascular endothelium with GDT might alter the postoperative inflammatory response and be responsible for the decreased complications with this therapy. METHODS: This trial was registered at ClinicalTrials.gov as NCT01681251. Forty patients undergoing elective open repair of their abdominal aortic aneurysm, 18 years of age and older, were randomized to an interventional arm with GDT targeting stroke volume variation with an arterial pulse contour cardiac output monitor, or control, where fluid therapy was administered at the discretion of the attending anesthesiologist. We measured levels of several inflammatory cytokines (C-reactive protein, Pentraxin 3, suppressor of tumorgenicity--2, interleukin-1 receptor antagonist, and tumor necrosis factor receptor-III) preoperatively and at several postoperative time points to determine if there was a difference in inflammatory response. We also assessed each group for a composite of postoperative complications. RESULTS: Twenty patients were randomized to GDT and twenty were randomized to control. Length of stay was not different between groups. Intervention patients received less crystalloid and more colloid. At the end of the study, intervention patients had a higher cardiac index (3.4 ± 0.5 vs. 2.5 ± 0.7 l/minute per m(2), p < 0.01) and stroke volume index (50.1 ± 7.4 vs. 38.1 ± 9.8 ml/m(2), p < 0.01) than controls. There were significantly fewer complications in the intervention than control group (28 vs. 12, p = 0.02). The length of hospital and ICU stay did not differ between groups. There was no difference in the levels of inflammatory cytokines between groups. CONCLUSIONS: Despite being associated with fewer complications and improved hemodynamics, there was no difference in the inflammatory response of patients treated with GDT. This suggests that the clinical benefit of GDT occurs in spite of a similar inflammatory burden. Further work needs to be performed to delineate the mechanism of benefit of GDT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01681251 . Registered 18 May 2011.

Ebola virus disease: an update for anesthesiologists and intensivists.

PURPOSE: Ebola virus disease (EVD) is a viral hemorrhagic fever that is highly transmissible and all too often rapidly fatal. Recent outbreaks in West Africa reveal that this infection has the potential to be transmitted worldwide. Anesthesiologists and intensivists, due to their training in the management of the critically ill, may be called upon to assist in the management of these patients. The focus of this brief review is on the epidemiology, pathogenesis, and management of patients with EVD. SOURCE: Review of the current literature. PRINCIPAL FINDINGS: Ebola virus disease causes severe diarrhea, electrolyte disturbances and other major end-organ dysfunction. Early aggressive resuscitation may reduce the mortality of this disease. There is presently no available vaccine nor cure, with experimental therapies having yielded limited success. Personal protective equipment (PPE) is necessary for all patient contact, and enhanced PPE is required for all aerosol-generating medical procedures. CONCLUSION: Anesthesiologists and intensivists may be called upon to manage patients with EVD. It is important that these clinicians have an appreciation for the epidemiology and pathogenesis of this disease and for the proper utilization of PPE when treating these patients.

Ethical concerns for anesthesiologists during an Ebola threat.

PURPOSE: The World Health Organization has proclaimed the current Ebola outbreak as a public health emergency. If an outbreak of Ebola should occur in Canada, anesthesiologists and anesthesia departments may be called upon to respond. The purpose of this review is to highlight and discuss potential ethical concepts that may be relevant to anesthesiologists. SOURCE: A thorough literature search was conducted using a variety of MEDLINE® sources, and we used Stand on Guard for Thee. Ethical Considerations in Preparedness Planning for Pandemic Influenza, a report by The University of Toronto Joint Centre for Bioethics Pandemic Influenza Working Group, as the framework for our review. PRINCIPAL FINDINGS: Two groups of ethical concerns were identified. The first group relates to public health ethics, which analyzes the morality of public health interventions, and the second group relates to medical ethics, particularly to "the duty to care". The Canadian Medical Association Code of Ethics is vague in the description of duties of physicians who may respond to high-risk contagious diseases. CONCLUSIONS: Government, public health authorities, and anesthesia departments need to be prepared to respond to an outbreak of Ebola. Anesthesiologists have a skill that is suited to treat the complications of Ebola virus disease, and in case they are called for duty, anesthesiologists should be aware of the ethical concerns of treating a highly contagious communicable disease.

Acute Kidney Injury in Patients Undergoing Open Abdominal Aortic Aneurysm Repair: A Pilot Observational Trial.

OBJECTIVES: Acute kidney injury (AKI) is a frequent complication after open repair of abdominal aortic aneurysms (AAA). Little research has been done to determine whether intraoperative hemodynamic events may precipitate AKI. Novel biomarkers also may aid in the earlier diagnosis of AKI. DESIGN: A pilot prospective observational trial. SETTING: A single tertiary academic medical center. PARTICIPANTS: Participants were 40 adult patients undergoing open repair of infrarenal AAA. INTERVENTIONS: Intraoperative hemodynamic monitoring of heart rate, mean arterial pressure, central venous pressure, and cardiac index was performed on a continuous basis. Blood samples were obtained at baseline and at 24 hours postoperatively for inflammatory biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL). MEASUREMENTS AND MAIN RESULTS: AKI occurred in 20% of patients (8 of 40). Hypotension, including duration (defined as the length of time mean arterial pressure was<65 mmHg) and magnitude (the area under the curve of a mean arterial pressure<65 mmHg), was the only factor associated with postoperative AKI. Urinary NGAL at the conclusion of surgery had excellent ability to predict the development of AKI (area under the curve 0.84, 95% confidence interval = 0.70-0.97). The cytokines pentraxin 3 (PTX3), interleukin-1 receptor antagonist (IL1-RA), macrophage chemotactic protein (MCP), suppressor of tumorigenicity 2 (ST-2), and interleukin-10 (IL-10) also had good ability to predict the development of AKI in the immediate postoperative period. CONCLUSIONS: AKI occurs frequently in patients undergoing open repair of AAA. Intraoperative hypotension was the only factor that predicted the development of subsequent AKI. Urinary NGAL and several novel inflammatory biomarkers demonstrated good ability to predict its development. Novel biomarkers also may aid in the early diagnosis of AKI.

Identification of four latent classes of acute respiratory distress syndrome using PaO2/FIO2 ratio: an observational cohort study.

Biological phenotypes in patients with the acute respiratory distress syndrome (ARDS) have previously been described. We hypothesized that the trajectory of PaO2/FIO2 ratio could be used to identify phenotypes of ARDS. We used a retrospective cohort analysis of an ARDS database to identify latent classes in the trajectory of PaO2/FIO2 ratio over time. We included all adult patients admitted to an intensive care unit who met the Berlin criteria for ARDS over a 4-year period in tertiary adult intensive care units in Manitoba, Canada. Baseline demographics were collected along with the daily PaO2/FIO2 ratio collected on admission and on days 1-7, 14 and 28. We used joint growth mixture modeling to test whether ARDS patients exhibit distinct phenotypes with respect to both longitudinal PaO2/FIO2 ratio and survival. The resulting latent classes were compared on several demographic variables. In our study group of 209 patients, we found that four latent trajectory classes of PaO2/FIO2 ratio was optimal. These four classes differed in their baseline PaO2/FIO2 ratio and their trajectory of improvement during the 28 days of the study. Despite similar baseline characteristics the hazard for death for the classes differed over time. This difference was largely driven by withdrawal of life sustaining therapy in one of the classes. Latent classes were identified in the trajectory of the PaO2/FIO2 ratio over time, suggesting the presence of different ARDS phenotypes. Future studies should confirm the existence of this finding and determine the cause of mortality differences between classes.

Role of the venous return in critical illness and shock: part II-shock and mechanical ventilation.

OBJECTIVE: To provide a conceptual and clinical review of the physiology of the venous system as it is related to cardiac function in health and disease. DATA: An integration of venous and cardiac physiology under normal conditions, critical illness, and resuscitation. SUMMARY: The usual clinical teaching of cardiac physiology focuses on left ventricular pathophysiology and pathology. Due to the wide array of shock states dealt with by intensivists, an integrated approach that takes into account the function of the venous system and its interaction with the right heart may be more useful. In part II of this two-part review, we describe the physiology of venous return and its interaction with the right heart function as it relates to mechanical ventilation and various shock states including hypovolemic, cardiogenic, obstructive, and septic shock. In particular, we demonstrate how these shock states perturb venous return/right heart interactions. We also show how compensatory mechanisms and therapeutic interventions can tend to return venous return and cardiac output to appropriate values. CONCLUSION: An improved understanding of the role of the venous system in pathophysiologic conditions will allow intensivists to better appreciate the complex circulatory physiology of shock and related therapies. This should enable improved hemodynamic management of this disorder.

The role of venous return in critical illness and shock-part I: physiology.

OBJECTIVE: To provide a conceptual and clinical review of the physiology of the venous system as it is relates to cardiac function in health and disease. DATA: An integration of venous and cardiac physiology under normal conditions, critical illness, and resuscitation. SUMMARY: The usual teaching of cardiac physiology focuses on left ventricular function. As a result of the wide array of shock states with which intensivists contend, an approach that takes into account the function of the venous system and its interaction with the right and left heart may be more useful. This two-part review focuses on the function of the venous system and right heart under normal and stressed conditions. The first part describes the basic physiology of the venous system, and part two focuses on the role of the venous system in different pathophysiologic states, particularly shock. CONCLUSION: An improved understanding of the role of the venous system in health and disease will allow intensivists to better appreciate the complex circulatory physiology of shock and may allow for better hemodynamic management of this disorder.

Cerebral oxygen desaturation during one-lung ventilation: correlation with hemodynamic variables.

PURPOSE: Cerebral desaturation occurs frequently in patients undergoing one-lung ventilation for thoracic surgery. The mechanism of this desaturation is unclear regarding its etiology. The objective of this study was to investigate whether or not decreases in cerebral oxygen saturation associated with one-lung ventilation were a consequence of decreased cardiac output. METHODS: A blinded observational study was conducted in 23 patients undergoing one-lung ventilation with thoracic surgery. Eighteen patients completed the study. Cerebral oxygen saturation was monitored using near-infrared spectroscopy (FORE-SIGHT(®) monitor). Invasive blood pressure was monitored and hemodynamic variables were interrogated using the FloTrac(®) system. Anesthesia was maintained with sevoflurane with a F(i)O(2) of 1.0. Post-hoc analysis involved a comparison between baseline and integrated changes in cerebral saturation, heart rate, stroke index, cardiac index, and stroke volume variability. RESULTS: All patients showed cerebral desaturation from a baseline of two-lung ventilation in the lateral decubitus position following institution of one-lung ventilation. The cardiac index was stable at these times, but with one-lung ventilation, the heart rate decreased and the stroke index increased to maintain a stable product. The integral of heart rate × time was inversely correlated with the integral of cerebral desaturation × time (linear regression analysis; P = 0.02; (df) = 16)). CONCLUSIONS: Cerebral oxygen desaturation was universal during one-lung ventilation in this study. There was no correlation between cerebral desaturation and cardiac output or other hemodynamic variables.

Tidal volume during 1-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: The selection of tidal volumes for 1-lung ventilation remains unclear, because there exists a trade-off between oxygenation and risk of lung injury. We conducted a systematic review and meta-analysis to determine how oxygenation, compliance, and clinical outcomes are affected by tidal volume during 1-lung ventilation. METHODS: A systematic search of MEDLINE and EMBASE was performed. A systematic review and random-effects meta-analysis was conducted. Pooled mean difference estimated arterial oxygen tension, compliance, and length of stay; pooled odds ratio was calculated for composite postoperative pulmonary complications. Risk of bias was determined using the Cochrane risk of bias and Newcastle-Ottawa tools. RESULTS: Eighteen studies were identified, comprising 3693 total patients. Low tidal volumes (5.6 [±0.9] mL/kg) were not associated with significant differences in partial pressure of oxygen (-15.64 [-88.53-57.26] mm Hg; P = .67), arterial oxygen tension to fractional intake of oxygen ratio (14.71 [-7.83-37.24]; P = .20), or compliance (2.03 [-5.22-9.27] mL/cmH2O; P = .58) versus conventional tidal volume ventilation (8.1 [±3.1] mL/kg). Low versus conventional tidal volume ventilation had no significant impact on hospital length of stay (-0.42 [-1.60-0.77] days; P = .49). Low tidal volumes are associated with significantly decreased odds of pulmonary complications (pooled odds ratio, 0.40 [0.29-0.57]; P < .0001). CONCLUSIONS: Low tidal volumes during 1-lung ventilation do not worsen oxygenation or compliance. A low tidal volume ventilation strategy during 1-lung ventilation was associated with a significant reduction in postoperative pulmonary complications.

The Incidence and Magnitude of Cerebral Desaturation in Traumatic Brain Injury: An Observational Cohort Study.

BACKGROUND: Cerebral ischemia in patients with traumatic brain injury (TBI) may propagate secondary neurological injury. Episodes of cerebral ischemia can be revealed through the use of cerebral oximetry monitoring. The objective of this study was to determine the incidence and severity of regional cerebral oxygen (rSO2) desaturation (rSO2<65%) in patients with severe TBI. Secondary outcomes included changes in other monitoring parameters associated with cerebral desaturation. MATERIALS AND METHODS: In this single-center prospective observational cohort study, cerebral oximetry data were collected continuously for up to 72 hours in 18 adult patients with a diagnosis of severe nonpenetrating TBI who were being mechanically ventilated and undergoing intracranial pressure (ICP) monitoring an in intensive care unit in Canada. Mean arterial pressure (MAP), ICP, and cerebral perfusion pressure were collected at 5-minute intervals during the study period. RESULTS: Twelve of 18 (67%) patients experienced an episode of cerebral desaturation. The median (interquartile range) nadir rSO2 was 57% (51% to 62%). The duration of desaturation was 265 (57 to 1277) minutes or 8.1% (2.6% to 26.0%) of recording time. In all patients, a linear regression analysis of the area under threshold of 65% for rSO2 was moderately correlated with the area above an ICP threshold of 20 mm Hg (R2=0.52; P<0.01). Similarly, there was a modest correlation between rSO2 and MAP (R2=0.41; P<0.01). These relationships also held true for those patients who experienced cerebral desaturation. Patients having episodes of ICP >20 mm Hg were 6 times more likely to have a cerebral desaturation (relative risk: 6.0; 95% confidence interval: 1.3-34.7). CONCLUSIONS: Cerebral desaturations occur frequently in patients with severe TBI, and their duration can be protracted. Episodes of desaturation were moderately correlated with increased ICP and decreased MAP.

Practical lessons from the first outbreaks: clinical presentation, obstacles, and management strategies for severe pandemic (pH1N1) 2009 influenza pneumonitis.

During the initial spring wave of novel influenza pH1N1 (2009), several North American cities experienced localized epidemics that served as a harbinger of the larger second Fall wave of infection. The city of Winnipeg, the capital of the province of Manitoba in central Canada, was one of the first in North America to deal with a rapid presentation of large numbers of patients requiring critical care services resulting from pandemic (pH1N1) 2009 influenza-associated respiratory failure. Mexico City, Orlando, FL, and Salt Lake City, UT, were other Northern Hemisphere sites of heavy disease activity during the spring wave of the pandemic. This article is written in a narrative format that allows the reader to understand the problems (both major and mundane, anticipated and unexpected) experienced by healthcare workers in these sites during this pandemic. Descriptions cover a range of issues and difficulties that caused significant stress to the operations of intensive care units in these cities. We hope to offer some insight into potential pitfalls and problems that may be experienced by other centers and provide some potential approaches to addressing these issues.

Positive end-expiratory pressure and recruitment maneuvers during one-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: It is unclear how positive end-expiratory pressure (PEEP) and recruitment maneuvers impact patients during one-lung ventilation (OLV). We conducted a systematic review and meta-analysis of the effect of lung recruitment and PEEP on ventilation and oxygenation during OLV. METHODS: A systematic review and random-effects meta-analysis were performed. Mean difference with standard deviation was calculated. Included studies were evaluated for quality and risk of bias using the Cochrane Risk of Bias tool and the modified Newcastle-Ottawa Score where appropriate. RESULTS: In total, 926 articles were identified, of which 16 were included in meta-analysis. Recruitment maneuvers increased arterial oxygen tension (PaO2) by 82 mm Hg [20, 144 mm Hg] and reduced dead-space by 5.9% [3.8, 8.0%]. PEEP increased PaO2 by 30.3 mm Hg [11.9, 48.6 mm Hg]. Subgroup analysis showed a significant increase in PaO2 (P = .0003; +35.4 mm Hg [16.2, 54.5 mm Hg]) with PEEP compared with no PEEP but no such difference in comparisons with PEEP-treated controls. No significant difference in PaO2 was observed between "high" and "low" PEEP-treated subgroups (P = .29). No significant improvement in PaO2 was observed for subgroups coadministered PEEP, lung recruitment, and low tidal volumes. PEEP was associated with a modest but statistically significant increase in compliance (P = .03; 4.33 mL/cmH2O [0.33, 8.32]). High risk of bias was identified in the majority of studies. Considerable heterogeneity was observed. CONCLUSIONS: Recruitment maneuvers and PEEP have physiologic advantages during OLV. The optimal use of PEEP is yet to be determined. The evidence is limited by heavy use of surrogate outcomes. Future studies with clinical outcomes are necessary to determine the impact of recruitment maneuvers and PEEP during OLV.

Adult cardiac surgery and the COVID-19 pandemic: Aggressive infection mitigation strategies are necessary in the operating room and surgical recovery.

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.

Adult Cardiac Surgery and the COVID-19 Pandemic: Aggressive Infection Mitigation Strategies Are Necessary in the Operating Room and Surgical Recovery.

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.

Minimally invasive cardiac output monitoring in the perioperative setting.

With advancing age and increased co-morbidities in patients, the need for monitoring devices during the perioperative period that allow clinicians to track physiologic variables, such as cardiac output (CO), fluid responsiveness and tissue perfusion, is increasing. Until recently, the only tool available to anesthesiologists to monitor CO was either a pulmonary artery catheter or transesophageal echocardiograph. These devices have their limitations and potential for morbidity. Several new devices (including esophageal Doppler monitors, pulse contour analysis, indicator dilution, thoracic bioimpedance and partial non-rebreathing systems) have recently been marketed which have the ability to monitor CO noninvasively and, in some cases, assess the patient's ability to respond to fluid challenges. In this review, we will describe these new devices including the technology, studies on their efficacy and the limitations of their use.

A brief report: the use of high-frequency oscillatory ventilation for severe pulmonary contusion.

BACKGROUND: Severe pulmonary contusions are a common cause of acute respiratory distress syndrome (ARDS) and are associated with significant morbidity. High frequency oscillatory ventilation (HFOV) is a ventilatory mode that employs a lung protective strategy consistent with the ARDSNet low tidal volume ventilation strategy and may result in reduced morbidity. The objective of this report is to examine the impact of HFOV on blunt trauma patients with severe pulmonary contusions who failed or were at a high risk of failing conventional mechanical ventilation. METHODS: We undertook a retrospective chart review of all patients at our institution who received HFOV for severe pulmonary contusions. Patients were placed on HFOV when their mean airway pressure (mP(aw)) surpassed 30 cm H2O and their FIO2 was greater than 0.6. Baseline demographic data including injury severity score (ISS), length of time requiring HFOV, total ventilator days, and inhospital mortality were collected. Serial determinations of oxygenation index (OI) and the PaO2/FIO2 ratio (P/F) were made up to 72 hours after initiation of HFOV. A linear mixed model was used to analyze the slope (beta) of the regression line of P/F versus time and that of OI versus time. RESULTS: Seventeen patients were identified who underwent HFOV for ARDS due primarily to pulmonary contusions. Mean ISS was 36.6, mean APACHE II score was 21.7, and the mean time before initiation of HFOV was 2.0 days. P/F increased significantly after HFOV was initiated (beta = 12.1; 95% confidence interval 7.9 to 16.4, p < 0.001). OI significantly decreased after HFOV implementation (beta = -1.8; 95% confidence interval -2.3 to -1.3, p < 0.001). Mortality rate was 17.6%. CONCLUSIONS: The early use of HFOV appears to be safe and efficacious in blunt trauma patients sustaining pulmonary contusions, and results in a rapid improvement in OI and the P/F ratio.