Richard H Kallet

UCSF University of California, San Francisco | UCSF · Department of Anesthesia and Perioperative Care

Background: Pneumonia from COVID-19 that results in ARDS may require invasive mechanical ventilation. This retrospective study assessed the characteristics and outcomes of subjects with COVID-19-associated ARDS versus ARDS (non-COVID) during the first 6 months of the COVID-19 pandemic in 2020. The primary objective was to determine whether mechani...

Purpose Potential negative implications associated with high respiratory rate (RR) are intrinsic positive end-expiratory pressure (PEEPi) generation, cardiovascular depression and possibly ventilator induced lung injury. Despite these negative consequences, optimal RR remains largely unknown. We hypothesized that without consideration of dynamics o...

Background: Post-extubation stridor (PES) is an imminently life-threatening event. Maximizing patient safety requires a systematic approach to screen patients for PES risk factors and a standardized test to evaluate that risk. This retrospective study of adult subjects was based on quality assurance data including standardized surveillance screeni...

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) in select individuals results in viral sepsis, pneumonia and hypoxemic respiratory failure, collectively known as coronavirus disease 2019 (COVID-19). In the early months of the pandemic the combination of novel disease presentation, enormous surges of critically ill pa...

Contemplating the future should be grounded in history. The rise of post-Polio intensive care units was inextricably related to mechanical ventilation. Critically-ill patients who developed acute respiratory failure often had "congestive atelectasis" (ie. a term used to describe ARDS prior to 1967). Initial mechanical ventilation strategies for tre...

Background: The generation of excessive inspiratory muscle pressure (Pmus) during assisted mechanical ventilation in patients with respiratory failure may result in acute respiratory muscle injury and/or fatigue, and exacerbate ventilator-induced lung injury. A readily available noninvasive surrogate measure of Pmus may help in titrating both mech...

Corona virus disease 2019 (COVID-19) represents the greatest medical crisis encountered in the young history of critical care and respiratory care. During the early months of the pandemic, when little was known about the virus, the acute hypoxemic respiratory failure it caused did not appear to fit conveniently or consistently into our classificati...

Background: ARDS mortality is lower among subjects participating in randomized controlled trials (RCTs) compared to subjects in observational studies. Excluding potential subjects with inordinately high mortality risk is necessary to prevent masking the impact of potentially effective treatments. We inquired whether observed mortality differed bet...

Numerous case reports, uncontrolled studies, and small randomized placebo-controlled trials have investigated the role of aerosolized opioids in the treatment of both dyspnea and pain. Recently, aerosolized furosemide was studied for the treatment of dyspnea. A direct effect on either pulmonary stretch receptors or irritant receptors has been propo...

Objectives: To evaluate the effects of inhaled epoprostenol and prone positioning, individually and in combination in mechanically ventilated patients with coronavirus disease 2019 and refractory hypoxemia. Design: Retrospective study. Setting: Academic hospital adult ICUs. Patients: Adult patients who received inhaled epoprostenol and prone...

Recruitment maneuvers in ARDS are used to improve oxygenation and lung mechanics by applying high airway pressures to reopen collapsed or obstructed peripheral airways and alveoli. In the early 1990s, recruitment maneuvers became a central feature of a variant form of lung-protective ventilation known as open-lung ventilation. This strategy is base...

Background: The ratio of end-tidal-to-arterial carbon dioxide tension (PETCO2/PaCO2) was recently suggested for monitoring pulmonary gas exchange in subjects with COVID-19 associated ARDS. Yet, no evidence was offered supporting that claim. Therefore, we evaluated whether PETCO2/PaCO2 might be relevant in assessing ARDS not associated with COVID-1...

Scientific research traditionally has been the domain of graduate school training, and it is based on higher cognitive levels associated with reflective thought. Such skills differ markedly from those needed to train competent respiratory therapists at the undergraduate level. Trainees at the undergraduate level need to acquire, comprehend, and app...

Implementation of ventilator bundles is associated with reductions in ventilator-associated pneumonia (VAP). However, the new surveillance model of ventilator-associated events (VAEs) has shifted the focus from VAP to objective, generalized signs of pulmonary decompensation not specific to VAP. This raises the question of whether the ventilator bun...

Background: The Berlin definition of ARDS does not account for nonpulmonary organ failure, which is a major determinant of outcome. We examined whether an increasing severity of hypoxemia across the Berlin definition classifications also corresponded with evidence of multiple organ dysfunction on the day of ARDS onset. We also examined the represe...

Rationale and objectives: Pulmonary dead space fraction is an independent predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is seldom utilized in practice. The Ventilatory ratio is a simple bedside index that can be calculated using routinely measured respiratory variables and is a measure of impaired ventilation. Venti...

Background: Common causes of acute respiratory distress syndrome (ARDS) include pneumonia, aspiration, non-pulmonary sepsis and trauma. Little is known about pulmonary mechanics and gas exchange in less-common etiologies of ARDS, which comprises 12-23% of cases. Our hospital's ARDS quality assurance database contained a substantial number of these...

This review describes the current understanding of the lungs' response to deforming stress under conditions of both normal physiology and acute lung injury. Several limiting assumptions are needed to infer lung parenchymal stress and strain from airway pressure, volume, and flow data from mechanically ventilated patients with injured lungs. These a...

Background: Spontaneous breathing trials (SBTs) and daily sedation interruptions (DSIs) reduce both the duration of mechanical ventilation and ICU length of stay (LOS). The impact of these practices in patients with ARDS has not previously been reported. We examined whether implementation of SBT/DSI protocols reduce duration of mechanical ventilat...

Background: In ARDS, elevated pulmonary dead-space fraction (VD/VT) is a particularly strong indicator of mortality risk. Whether the magnitude of VD/VT is modified by the underlying etiology of ARDS and whether this influences the strength of its association with mortality remains unknown. We sought to elucidate the impact of ARDS etiology on VD/...

Background: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and r...

Background: Accurately measuring the partial pressure of end-tidal CO2 (PETCO2 ) in non-intubated patients is problematic due to dilution of expired CO2 at high O2 flows and mask designs that may either cause CO2 rebreathing or inadequately capture expired CO2. We evaluated the performance of 2 capnographic O2 masks (Cap-ONE and OxyMask) against a...

To the Editor: In a recent issue of Respiratory Care, Mireles-Cabodevila and Kacmarek[1][1] did an excellent job reviewing the pros and cons of airway pressure release ventilation (APRV). The paper and the discussion session raised serious concerns about ARPV, particularly regarding imposed work

Oxygen is both lifesaving and toxic. Appropriate use of oxygen aims to provide a balance between the two effects. Although local oxygen toxicity to the lung is well accepted, recent evidence has called into question the negative consequences of hyperoxemia in other organ beds. Hyperoxia following cardiac arrest, traumatic brain injury, and stroke h...

Functional residual capacity (FRC) is essentially the alveolar volume and a determinant of both oxygenation and respiratory system compliance (CRS). ARDS decreases FRC, and sufficient PEEP restores FRC; thus, assessments of PEEP by its impact on oxygenation and CRS are intimately linked. PEEP also can ameliorate or aggravate ventilator-induced lung...

Negative pressure pulmonary edema (NPPE) or post-obstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvas...

Prone position (PP) has been used since the 1970s to treat severe hypoxemia in patients with ARDS because of its effectiveness at improving gas exchange. Compared with the supine position (SP), placing patients in PP effects a more even tidal volume distribution, in part, by reversing the vertical pleural pressure gradient, which becomes more negat...

Ventilator-associated pneumonia (VAP) is an acquired infection related primarily to the consequences of prolonged endotracheal intubation. It is considered the most important infectious challenge in the critical care setting. Preventable complications of hospital care are considered an important source of wasted health-care costs believed to consum...

In the early years of lung-protective ventilation, it was thought that limiting plateau pressure (Pplat), a signifier of alveolar stress, was important for improving survival in patients with ARDS. However, there were no clinical data and no agreement on the limit. A 1993 consensus conference

Background: Little is known about the relationship between body temperature and outcomes in patients with acute respiratory distress syndrome (ARDS). A better understanding of this relationship may provide evidence for fever suppression or warming interventions, which are commonly applied in practice. Objective: To examine the relationship between...

To test the association between pulmonary dead-space fraction (VD/VT) and mortality in patients with ARDS (Berlin Definition, PaO2/FiO2 ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. Prospective, multi-center study. Medical-surgical intensive care units in the United States. 126 ALI patients...

Mechanically ventilated patients in respiratory failure often require adjunct therapies to address special needs such as inhaled drug delivery to alleviate airway obstruction, treat pulmonary infection, or stabilize gas exchange, or therapies that enhance pulmonary hygiene. These therapies generally are supportive in nature rather than curative. Cu...

For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to invasive mechanical ventilation, noninvasive ventilation, and cystic...

Prolonged breathing of very high F(IO(2)) (F(IO(2)) ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of F(IO(2)), is usually fatal. The severity of HALI is directly proportional to P(O(2)) (particularly above 450 mm Hg, or an F(IO(2)) of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts o...

Several recent studies have advanced our understanding of dead-space ventilation in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). They have demonstrated the utility of measuring physiologic dead-space-to-tidal volume ratio (VD/VT) and related variables in assessing outcomes as well as therapeutic interventions. The...

During the past decade of research on acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) there has been heightened interest in measuring physiologic dead-space fraction (VD/VT). Since ARDS first was described 44 years ago, the primary focus on gas exchange abnormalities concerned

An interesting study by Tulaimat and Mokhlesi[1][1] regarding the accuracy and reliability of extubation decisions that recently appeared in the Journal merits additional comment. The implicit study question is whether an informed decision to extubate following a successful spontaneous breathing

A study published in the previous issue of Critical Care demonstrates that measurement of the pulmonary dead-space fraction is superior to hypoxemia as an indicator of a favorable physiologic response to prone positioning in patients with severe acute respiratory distress syndrome. These results add to the growing evidence supporting the clinical a...

β₂-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. This clinical trial was designed to test the hypothesis that an aerosolized β₂-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). We conducted a multicenter, randomized, placebo-controlled clinica...

Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We stu...

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are sequelae of severe trauma. It is unknown if certain races are at greater risk of developing ALI/ARDS, and once established, if there are racial differences in the severity of lung injury or mortality. Retrospective cohort study of 4,397 trauma patients (1,831 Caucasians, 871...

Since the early 1970s there has been an ongoing debate regarding the wisdom of promoting unassisted spontaneous breathing throughout the course of critical illness in patients with severe respiratory failure. The basis of this debate has focused on the clinical relevance of opposite problems. Historically, the term "disuse atrophy" has described a...

Airway pressure release ventilation (APRV) and bi-level positive airway pressure (BIPAP) are proposed to reduce patient work of breathing (WOB) sufficiently and to obviate issues related to patient-ventilator synchrony, so that spontaneous breathing can be maintained throughout the course of acute lung injury (ALI). Thus, APRV/BIPAP should reduce r...

To test the hypothesis that the concentration of angiopoietin-2 relative to angiopoietin-1 may be a useful biological marker of mortality in acute lung injury patients. We also tested the association of concentration of angiopoietin-2 relative to angiopoietin-1 with physiologic and biological markers of activated endothelium. Prospective, observati...

We report a complicated case of acute respiratory distress syndrome (ARDS) from severe sepsis, in which we measured the ratio of physiologic dead space to tidal volume (V(D)/V(T)) with volumetric capnography prior to, during, and after therapy with human recombinant activated protein C. Previous studies hypothesized that early in ARDS, elevated V(D...

Venous thromboembolic events (VTE) remain a major cause of morbidity and mortality after trauma. Fondaparinux, a synthetic, nonheparin drug, has shown promise in reducing VTE in orthopaedic patients, but has not previously been studied in trauma patients. The goal of this study was to determine the safety and efficacy of fondaparinux when incorpora...

It has been almost 15 years since the National Institutes of Health created the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDS Network) and nearly a decade since the completion of the landmark low-tidal volume (V T) trial. In retrospect, the ARDS Network had a profound impact on the design and conduct of clinical trials in critic...

This conference brought together experts on noninvasive ventilation (NIV) to discuss and debate the advances in evidence and technology over the past decade. A major impetus for the conference was that many institutions have not systematically integrated NIV into their clinical practice, despite mounting, high-level evidence supporting its effectiv...

The physiologic effects of noninvasive ventilation (NIV) on work of breathing (WOB) and breathing pattern, respiratory-system mechanics, and hemodynamic function were examined via a literature review of clinical studies done between 1990 and 2008. Forty-one relevant studies were found; the majority examined patients with chronic obstructive pulmona...

Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary p...

Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A...

Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. To test the efficacy of activated protein C (APC) as a therapy for patients with ALI...

The spontaneous breathing pattern and its relationship to compliance, resistance, and work of breathing (WOB) has not been examined in patients with acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). Clinically, the ratio of respiratory frequency to tidal volume (f/VT) during spontaneous breathing may reflect adaptation to alter...

Numerous case reports, uncontrolled studies, and small randomized placebo-controlled trials have investigated the role of aerosolized opioids in the treatment of both dyspnea and pain. Recently, aerosolized furosemide was studied for the treatment of dyspnea. A direct effect on either pulmonary stretch receptors or irritant receptors has been propo...

Postobstructive pulmonary edema is a well-recognized complication of upper airway obstruction. The mechanisms of edema formation are unclear and may be due to increased hydrostatic forces generated by high negative inspiratory pressure or by increased permeability of the alveolar capillary membrane. Measurement of the edema fluid/plasma protein rat...

Lung recruitment maneuvers are being used in the management of acute lung injury and acute respiratory distress syndrome, but recruitment maneuvers are controversial. The proponents argue that when properly applied to appropriately selected patients, they are effective and can be safely applied. The expectation is that the recruitment maneuver will...