Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model.

INTRODUCTION: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation. METHODS: Thirteen human patients with isolated TBI were enrolled and randomized to receive either placebo or iNO with measured outcomes including pulmonary parameters, blood gas data, and intracranial pressure (ICP) /perfusion. To complement this study, a porcine model of TBI (including 10 swine) was utilized with measured outcomes of brain tissue blood flow and oxygenation, ventilator parameters, and blood gas data both after administration and following drug removal and clearance. RESULTS: There were no clinically significant changes in pulmonary parameters in either the human or porcine arm following administration of iNO when compared to either the placebo group (human arm) or the internal control (porcine arm). Analysis of pooled human data demonstrated the preservation of alveolar recruitment in TBI patients. There were no clinically significant changes in human ICP or cerebral perfusion pressure following iNO administration compared to controls. CONCLUSIONS: iNO had no significant effect on clinically relevant pulmonary parameters or ICPs following TBI in both human patients and a porcine model. The pressure-based recruitment of the human lungs following TBI was preserved. Further investigation will be needed to determine the degree of utility of iNO in the setting of hypoxia after polytrauma.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

Antimicrobial Coating Prevents Ventilator-Associated Pneumonia in a 72 hour Large Animal Model.

BACKGROUND: The primary goal of this study was to demonstrate that endotracheal tubes coated with antimicrobial lipids plus mucolytic or antimicrobial lipids with antibiotics plus mucolytic would significantly reduce pneumonia in the lungs of pigs after 72 hours of continuous mechanical ventilation compared to uncoated controls. MATERIALS AND METHODS: Eighteen female pigs were mechanically ventilated for up to 72 hours through uncoated endotracheal tubes, endotracheal tubes coated with the antimicrobial lipid, octadecylamine, and the mucolytic, N-acetylcysteine, or tubes coated with octadecylamine, N-acetylcysteine, doxycycline, and levofloxacin (6 pigs per group). No exogenous bacteria were inoculated into the pigs, pneumonia resulted from the pigs' endogenous oral flora. Vital signs were recorded every 15 minutes and arterial blood gas measurements were obtained for the duration of the experiment. Pigs were sacrificed either after completion of 72 hours of mechanical ventilation or just prior to hypoxic arrest. Lungs, trachea, and endotracheal tubes were harvested for analysis to include bacterial counts of lung, trachea, and endotracheal tubes, lung wet and dry weights, and lung tissue for histology. RESULTS: Pigs ventilated with coated endotracheal tubes were less hypoxic, had less bacterial colonization of the lungs, and survived significantly longer than pigs ventilated with uncoated tubes. Octadecylamine-N-acetylcysteine-doxycycline-levofloxacin coated endotracheal tubes had less bacterial colonization than uncoated or octadecylamine-N-acetylcysteine coated tubes. CONCLUSION: Endotracheal tubes coated with antimicrobial lipids plus mucolytic and antimicrobial lipids with antibiotics plus mucolytic reduced bacterial colonization of pig lungs after prolonged mechanical ventilation and may be an effective strategy to reduce ventilator-associated pneumonia.

Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.

Development and Reporting of Prediction Models: Guidance for Authors From Editors of Respiratory, Sleep, and Critical Care Journals.

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

Ketamine versus hydromorphone patient-controlled analgesia for acute pain in trauma patients.

BACKGROUND: It is unknown whether ketamine administered via patient-controlled analgesia (PCA) provides adequate analgesia while reducing opioid consumption in the traumatically injured patient. Differences in opioid consumption, pain scores, and adverse effects between ketamine and hydromorphone PCA were studied. MATERIALS AND METHODS: This is an investigator-initiated, single-center, double-blinded, randomized, pilot trial conducted from 2014 to 2016 at a level 1 trauma center. Nonintubated trauma patients in intensive care, who were receiving PCA, were randomized to ketamine or hydromorphone PCA plus opioid analgesics for breakthrough pain. RESULTS: Twenty subjects were randomized. There was no difference in median daily breakthrough opioid use (10 [0.63-19.38] mg versus 10 [4.38-22.5] mg, P = 0.55). Subjects in the ketamine group had lower median cumulative opioid use on therapy day 1 than the hydromorphone group (4.6 [2.5-15] mg versus 41.8 [31.8-50] mg, P < 0.001), as well as in the first 48 h (10 [3.3-15] mg versus 48.5 [32.1-67.5] mg, P < 0.001) and first 72 h (10 [4.2-15] mg versus 42.5 [31.7-65.2] mg, P < 0.001) of therapy. Daily oxygen supplementation requirements were lower in the ketamine group (0.5 [0-1.5] L/min versus 2 [0.5-3] L/min, P = 0.020). Hallucinations occurred more frequently in the ketamine group (40% versus 0%, P = 0.090). CONCLUSIONS: Ketamine PCA led to lower cumulative opioid consumption and lower oxygen supplementation requirements, though hallucinations occurred more frequently with use of ketamine. Additional studies are needed to investigate the tolerability of ketamine as an alternative to traditional opioid-based PCA.

Pre-hospital oxygen therapy.

Oxygen use in prehospital care is aimed at treating or preventing hypoxemia. However, excess oxygen delivery has important consequences in select patients, and hyperoxia can adversely impact outcome. The unique environment of prehospital care poses logistical and educational challenges. Oxygen therapy in prehospital care should be provided to patients with hypoxemia and titrated to achieve normoxemia. Changes to the current practice of oxygen delivery in prehospital care are needed.

Oxygen supplies in disaster management.

Mass casualty events and disasters, both natural and human-generated, occur frequently around the world and can generate scores of injured or ill victims in need of resources. Of the available medical supplies, oxygen remains the critical consumable resource in disaster management. Strategic management of oxygen supplies in disaster scenarios remains a priority. Hospitals have large supplies of liquid oxygen and a supply of compressed gas oxygen cylinders that allow several days of reserve, but a large influx of patients from a disaster can strain these resources. Most backup liquid oxygen supplies are attached to the main liquid system and supply line. In the event of damage to the main system, the reserve supply is rendered useless. The Strategic National Stockpile supplies medications, medical supplies, and equipment to disaster areas, but it does not supply oxygen. Contracted vendors can deliver oxygen to alternate care facilities in disaster areas, in the form of concentrators, compressed gas cylinders, and liquid oxygen. Planning for oxygen needs following a disaster still presents a substantial challenge, but alternate care facilities have proven to be valuable in relieving pressure from the mass influx of patients into hospitals, especially for those on home oxygen who require only an electrical source to power their oxygen concentrator.

COVID-19 Lessons Learned: Response to the Anticipated Ventilator Shortage.

Early in the COVID-19 pandemic predictions of a worldwide ventilator shortage prompted a worldwide search for solutions. The impetus for the scramble for ventilators was spurred on by inaccurate and often unrealistic predictions of ventilator requirements. Initial efforts looked simply at acquiring as many ventilators as possible from national and international sources. Ventilators from the Strategic National Stockpile were distributed to early hotspots in the Northeast and Northwest United States. In a triumph of emotion over logic, well-intended experts from other industries turned their time, talent, and treasure toward making a ventilator for the first time. Interest in shared ventilation (more than one patient per ventilator) was ignited by an ill-advised video on social media that ignored the principles of gas delivery in deference to social media notoriety. With shared ventilation, a number of groups mistook a physiologic problem for a plumbing problem. The United States government invoked the Defense Production Act to push automotive manufacturers to partner with existing ventilator manufacturers to speed production. The FDA granted emergency use authorization for "splitters" to allow shared ventilation as well as for ventilators and ancillary equipment. Rationing of ventilators was discussed in the lay press and medical literature but was never necessary in the US. Finally, planners realized that staff with expertise in providing mechanical ventilation were the most important shortage. Over 200,000 ventilators were purchased by the United States government, states, cities, health systems, and individuals. Most had little value in caring for patients with COVID-19 ARDS. This paper attempts to look at where miscalculations were made, with an eye toward what we can do better in the future.

Accuracy of Multiple Pulse Oximeters in Stable Critically Ill Patients.

BACKGROUND: An accurate SpO2 value is critical in order to optimally titrate oxygen delivery to patients and to follow oxygenation guidelines. Limited prospective data exist on real-world performance of pulse oximeters in critically ill patients. The objective of this study was to assess accuracy and bias of the SpO2 values measured by several oximeters in hospitalized subjects. METHODS: We included stable adults in the ICU with an arterial catheter in place. Main exclusion criteria were poor SpO2 signal and SpO2 > 96%. In each subject, we simultaneously evaluated 4 oximeters: Nonin (Plymouth, Minnesota) embedded in the FreeO2 device (OxyNov, Québec City, Québec, Canada), Masimo (Radical-7, Masimo, Irvine, California), Philips (FAST, Philips, Amsterdam, the Netherlands), and Nellcor (N-600, Medtronic, Minneapolis, Minnesota). Arterial blood gases were drawn and simultaneously each oximeters' SpO2 values were collected. SpO2 values were compared to the reference (arterial oxygen saturation [SaO2 ] value) to determine bias and accuracy. The ability for oximeters to detect hypoxemia and the impact of oximeters on oxygen titration were evaluated. RESULTS: We included 193 subjects (153 male, mean age 66 y) in whom 211 sets of measurements were performed. The skin pigmentation evaluated by Fitzpatrick scale showed 96.2% of subjects were light skin (types 1 and 2). One oximeter overestimated SaO2 (Philips, +0.9%), whereas the 3 others underestimated SaO2 (Nonin -3.1%, Nellcor -0.3%, Masimo -0.2%). SaO2 was underestimated with Nonin oximeter in 91.3% of the cases, whereas it was overestimated in 55.2% of the cases with Philips oximeter. Moderate hypoxemia (SaO2 86-90% or PaO2 55-60 mm Hg) was detected in 92, 33, 42, and 11% of the cases with Nonin, Nellcor, Masimo, and Philips, respectively. CONCLUSIONS: We found significant bias and moderate accuracy between the tested oximeters and the arterial blood gases in the studied population. These discrepancies may have important clinical impact on the detection of hypoxemia and management of oxygen therapy.

Modes to facilitate ventilator weaning.

Weaning comprises 40 percent of the duration of mechanical ventilation. Protocols to reduce weaning time and to identify candidates at the earliest possible moment have been introduced to reduce complications and costs. Increased demand for mechanical ventilation, an increase in the number of patients requiring prolonged ventilation, and resource/staffing issues have created an environment where automated weaning may play a role. A number of closed loop techniques have been introduced since the early 1990s, with increasing sophistication. Preliminary research has demonstrated mixed results. Current systems continue to be evaluated in different patient populations and environments. Automated weaning is part of the ICU armamentarium, and identification of the patient populations most likely to benefit needs to be further defined.

Lessons from the tip of the spear: medical advancements from Iraq and Afghanistan.

The conflicts in Iraq and Afghanistan have seen the advancement of combat medicine. The nature of the conflicts, with troops located in remote areas and faced with explosive ordinance designed to focus massive injuries on dismounted personnel, have forced military medical personnel to adapt accordingly. There has been a rekindling of interest in the use of tourniquets to stop exsanguination from extremity wounds, as well as in the transfusion of fresh whole blood from walking blood banks. These previously discarded techniques, born on battlefields long ago, have been refined and perfected and have led to an unprecedented survival for our wounded warriors. New developments in the field of applied hemostatic agents, damage control surgical techniques, and the implementation of an efficient evacuation system have also contributed to these results. The field of combat medicine has taken several concepts initially designed in civilian settings, such as temporary abdominal packing and vascular shunting, and adapted them to the military setting to provide state of the art trauma management to our troops in combat. In turn, developments in the resuscitation of the trauma patient, using increased blood and plasma products and less crystalloid, have been pioneered in conflict and transitioned to the civilian sector. Advancements made during the wars in Iraq and Afghanistan, as well as those still being developed, will shape the care of the injured patient, in both civilian and military settings, for the foreseeable future.

Use of a single ventilator to support 4 patients: laboratory evaluation of a limited concept.

INTRODUCTION: A mass-casualty respiratory failure event where patients exceed available ventilators has spurred several proposed solutions. One proposal is use of a single ventilator to support 4 patients. METHODS: A ventilator was modified to allow attachment of 4 circuits. Each circuit was connected to one chamber of 2 dual-chambered, test lungs. The ventilator was set at a tidal volume (V(T)) of 2.0 L, respiratory frequency of 10 breaths/min, and PEEP of 5 cm H(2)O. Tests were repeated with pressure targeted breaths at 15 cm H(2)O. Airway pressure, volume, and flow were measured at each chamber. The test lungs were set to simulate 4 patients using combinations of resistance (R) and compliance (C). These included equivalent C and R, constant R and variable C, constant C and variable R, and variable C and variable R. RESULTS: When R and C were equivalent the V(T) distributed to each chamber of the test lung was similar during both volume (range 428-442 mL) and pressure (range 528-544 mL) breaths. Changing C while R was constant resulted in large variations in delivered V(T) (volume range 257-621 mL, pressure range 320-762 mL). Changing R while C was constant resulted in a smaller variation in V(T) (volume range 418-460 mL, pressure range 502-554 mL) compared to only C changes. When R and C were both varied, the range of delivered V(T) in both volume (336-517 mL) and pressure (417-676 mL) breaths was greater, compared to only R changes. CONCLUSIONS: Using a single ventilator to support 4 patients is an attractive concept; however, the V(T) cannot be controlled for each subject and V(T) disparity is proportional to the variability in compliance. Along with other practical limitations, these findings cannot support the use of this concept for mass-casualty respiratory failure.

Respiratory Drive, Dyspnea, and Silent Hypoxemia: A Physiological Review in the Context of COVID-19.

Infection with SARS-CoV-2 in select individuals results in viral sepsis, pneumonia, and hypoxemic respiratory failure, collectively known as COVID-19. In the early months of the pandemic, the combination of novel disease presentation, enormous surges of critically ill patients, and severity of illness lent to early observations and pronouncements regarding COVID-19 that could not be scientifically validated owing to crisis circumstances. One of these was a phenomenon referred to as "happy hypoxia." Widely discussed in the lay press, it was thought to represent a novel and perplexing phenomenon: severe hypoxemia coupled with the absence of respiratory distress and dyspnea. Silent hypoxemia is the preferred term describing an apparent lack of distress in the presence of hypoxemia. However, the phenomenon is well known among respiratory physiologists as hypoxic ventilatory decline. Silent hypoxemia can be explained by physiologic mechanisms governing the control of breathing, breathing perception, and cardiovascular compensation. This narrative review examines silent hypoxemia during COVID-19 as well as hypotheses that viral infection of the central and peripheral nervous system may be implicated. Moreover, the credulous embrace of happy hypoxia and the novel hypotheses proposed to explain it has exposed significant misunderstandings among clinicians regarding the physiologic mechanisms governing both the control of breathing and the modulation of breathing sensations. Therefore, a substantial focus of this paper is to provide an in-depth review of these topics.

Shortages and Vulnerabilities of Hospital Oxygen Systems.

The COVID-19 pandemic has inundated hospitals with patients suffering from profound hypoxemia and placed a strain on health care systems around the world. Shortages of personnel, drugs, ventilators, and beds were predicted and, in many cases, came to fruition. As the pandemic wore on, there have been reports of impacts on hospital medical gas supply systems. Oxygen in particular has been a concern for hospitals in terms of supply and distribution. This article outlines procedures for estimating medical gas flow limitations within health care organizations and also methods for estimating gas consumption.

Disaster planning for pediatrics.

Natural and man-made disasters are inevitable and appear to be more common in the current age. Substantial time and effort have been invested and millions of dollars spent on disaster prevention and management. An important oversight in this planning has been the special needs of children. The vulnerability of children and their physiologic characteristics place them at increased risk during a disaster. Importantly, reunification with family and assurance of safety in this vulnerable group is a priority. This paper addresses issues related to pediatric needs, the medical system's shortcomings in caring for children, and recommendations for action.

Patient-ventilator interaction: the last 40 years.

Patient-ventilator synchrony is a complex issue affected by ventilator performance, patient characteristics, and the patient-ventilator interface. The history of patient-ventilator interaction includes avoidance of pharmacalogic paralysis, the development of spontaneous breathing systems, microprocessor technology to maximize interaction, and closed-loop control. While most clinicians agree that patient-ventilator synchrony is desirable, there remain no cause-and-effect data that asynchrony is associated with poor outcome.