Robert M. Kacmarek

A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial*

Objective:It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). Design:Randomized, controlled clinical trial. Setting:Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: España Study). Patients:All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained ≤200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV. Interventions:In the control group, tidal volume was 9–11 mL/kg of predicted body weight (PBW) and PEEP ≥5 cm H2O. In the Pflex/LTV group, tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70–100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg. Measurements and Main Results:The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). Conclusions:A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.

Intensive care unit quality improvement: A "how-to" guide for the interdisciplinary team*

Objective:Quality improvement is an important activity for all members of the interdisciplinary critical care team. Although an increasing number of resources are available to guide clinicians, quality improvement activities can be overwhelming. Therefore, the Society of Critical Care Medicine charged this Outcomes Task Force with creating a “how-to” guide that focuses on critical care, summarizes key concepts, and outlines a practical approach to the development, implementation, evaluation, and maintenance of an interdisciplinary quality improvement program in the intensive care unit. Data Sources and Methods:The task force met in person twice and by conference call twice to write this document. We also conducted a literature search on “quality improvement” and “critical care or intensive care” and searched online for additional resources. Data Synthesis and Overview:We present an overview of quality improvement in the intensive care unit setting and then describe the following steps for initiating or improving an interdisciplinary critical care quality improvement program: a) identify local motivation, support teamwork, and develop strong leadership; b) prioritize potential projects and choose the first target; c) operationalize the measures, build support for the project, and develop a business plan; d) perform an environmental scan to better understand the problem, potential barriers, opportunities, and resources for the project; e) create a data collection system that accurately measures baseline performance and future improvements; f) create a data reporting system that allows clinicians and others to understand the problem; g) introduce effective strategies to change clinician behavior. In addition, we identify four steps for evaluating and maintaining this program: a) determine whether the target is changing with periodic data collection; b) modify behavior change strategies to improve or sustain improvements; c) focus on interdisciplinary collaboration; and d) develop and sustain support from the hospital leadership. We also identify a number of online resources to complement this overview. Conclusions:This Society of Critical Care Medicine Task Force report provides an overview for clinicians interested in developing or improving a quality improvement program using a step-wise approach. Success depends not only on committed interdisciplinary work that is incremental and continuous but also on strong leadership. Further research is needed to refine the methods and identify the most cost-effective means of improving the quality of health care received by critically ill patients and their families.

Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.

Background:Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response. Methods:Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days. Results:Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 ± 7 to 30 ± 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 ± 36 to 149 ± 38 mmHg) and the venous admixture decreased (from 31.2 ± 5.5 to 28.2 ± 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm NO effectively reduced mean pulmonary artery pressure (38 ± 7 vs. 31 ± 6 mmHg) and increased arterial oxygen tension (79 ± 10 vs. 114 ± 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r=-0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r=-0.78). Conclusions:Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.

Hemodynamic effects of inhaled nitric oxide in heart failure.

OBJECTIVES This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. BACKGROUND Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Non-selective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. METHODS Systemic and pulmonary hemodynamic measurement were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. RESULTS Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/- 14 dynes.s.cm-5) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm-5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. CONCLUSIONS Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome

Background: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. Methods: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2≤ 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO2 trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI–24 h if the PaO2/FIO2 was > 150 mmHg with PEEP = 5 cmH2O, and ARDS–24 h if the PaO2 /FIO2 was ≤ 150 mmHg with PEEP ≥ 5 cmH2O. Results: Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO2 response to PEEP 5 cmH2O allowed the separation of our patients into two different groups: 31 patients met our ALI–24 h criteria (PaO2/FIO2 > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS–24 h criteria (PaO2/FIO2≤ 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO2/FIO2 ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Conclusions: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted.

Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy.

Objective:Although noninvasive positive pressure ventilation (NPPV) is a widely accepted treatment for some patients with acute respiratory failure, the use of NPPV in patients who have decided to forego endotracheal intubation is controversial. Therefore, the Society of Critical Care Medicine charged this Task Force with developing an approach for considering use of NPPV for patients who choose to forego endotracheal intubation. Data Sources and Methods:The Task Force met in person once, by conference call twice, and wrote this document during six subsequent months. We reviewed English-language literature on NPPV for acute respiratory failure. Synthesis and Overview:The use of NPPV for patients with acute respiratory failure can be classified into three categories: 1) NPPV as life support with no preset limitations on life-sustaining treatments, 2) NPPV as life support when patients and families have decided to forego endotracheal intubation, and 3) NPPV as a palliative measure when patients and families have chosen to forego all life support, receiving comfort measures only. For each category, we reviewed the rationale and evidence for NPPV, key points to communicate to patients and families, determinants of success and failure, appropriate healthcare settings, and alternative approaches if NPPV fails to achieve the original goals. Conclusions:This Task Force suggests an approach to use of NPPV for patients and families who choose to forego endotracheal intubation. NPPV should be applied after careful discussion of the goals of care, with explicit parameters for success and failure, by experienced personnel, and in appropriate healthcare settings. Future studies are needed to evaluate the clinical outcomes of using NPPV for patients who choose to forego endotracheal intubation and to examine the perspectives of patients, families, and clinicians on use of NPPV in these contexts.

Low concentrations of nitric oxide increase oxygen affinity of sickle erythrocytes in vitro and in vivo.

The hallmark of sickle cell disease (SCD) is the polymerization of deoxygenated sickle hemoglobin (HbS). In SCD patients, one strategy to reduce red blood cell (RBC) sickling is to increase HbS oxygen affinity. Our objective was to determine if low concentrations of nitric oxide (NO) gas would augment the oxygen affinity of RBCs containing homozygous HbS (SS). Blood containing normal adult hemoglobin (AA) or SS RBCs was incubated in vitro in the presence of varying concentrations of NO up to 80 ppm, and oxygen dissociation curves (ODCs) were measured. In addition, blood was obtained from three AA and nine SS volunteers, before and after breathing 80 ppm NO in air for 45 min, and the ODCs were measured. Exposure of SS RBCs to 80 ppm NO in vitro for 5 min or longer decreased the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen (P50), an average of 15% (4.8+/-1.7 mmHg mean+/-SE; P < 0.001). The increase in SS RBC oxygen affinity correlated with the NO concentration. The P50 of AA RBCs was unchanged (P > 0.1) by 80 ppm NO. In SS volunteers breathing 80 ppm NO for 45 min, the P50 decreased (P < 0.001) by 4.6+/-2.0 mmHg. 60 min after NO breathing was discontinued, the RBC P50 remained decreased in five of seven volunteers in whom the ODC was measured. There was no RBC P50 change (P > 0.1) in AA volunteers breathing NO. Methemoglobin (Mhb) remained low in all subjects breathing NO (SS Mhb 1.4+/-0.5%), and there was no correlation (r = 0.02) between the reduction in P50 and the change in Mhb. Thus, low concentrations of NO augment the oxygen affinity of sickle erythrocytes in vitro and in vivo without significant Mhb production. These results suggest that low concentrations of NO gas may offer an attractive new therapeutic model for the treatment of SCD.

Noninvasive positive pressure ventilation reverses acute respiratory failure in select "do-not-intubate" patients.

Objective:To determine the outcome from the use of noninvasive positive pressure ventilation (NPPV) in “do-not-intubate” (DNI) patients in acute respiratory failure. Design:Prospective observational study. Setting:University-affiliated large medical center. Patients:All patients with DNI status who received NPPV for a 1-yr period. Interventions:None. Measurements and Main Results:Demographic, physiologic, and laboratory data were collected before initiation, 2 hrs after initiation, and each morning and evening for as long as NPPV was provided. Data were recorded on 137 episodes of acute respiratory failure in 131 DNI patients. Hospital mortality rate was 37.5% in 24 patients with an exacerbation of chronic obstructive pulmonary disease (COPD), 39% in 28 patients with acute cardiogenic pulmonary edema, 68% in nine patients with non-COPD hypercapnic ventilatory failure, 77% in 13 postextubation respiratory failure patients, and 86% in 57 patients with hypoxemic respiratory failure. Advanced cancer was present in 40 patients and was associated with increased risk of death (85% mortality rate, p = .002). A score based on the Simplified Acute Physiology Score (SAPS) II and serum albumin level calculated before NPPV was predictive of hospital outcome. Conclusions:NPPV is successful in reversing acute respiratory failure and preventing hospital mortality in DNI patients with COPD and cardiogenic pulmonary edema but not in patients with postextubation failure, hypoxemic respiratory failure, or end-stage cancer. An easy-to-calculate score combining SAPS II and serum albumin level is a good prediction of outcome in DNI patients receiving NPPV.

A protocol for high-frequency oscillatory ventilation in adults: Results from a roundtable discussion*

Objective:Ventilator settings typically used for high-frequency oscillatory ventilation (HFO) in adults provide acceptable gas exchange but may not take best advantage of its lung-protective aspects. We provide guidelines for HFO in adults with acute respiratory distress syndrome that should optimize the lung-protective characteristics of this ventilation mode. Design:Roundtable discussions, iterative revisions, and consensus. Setting:Five academic medical centers. Patients:Not applicable. Interventions:Participants addressed how to best maintain ventilation through combinations of oscillation pressure amplitude, frequency, and the use of an endotracheal tube cuff leak, and to maintain oxygenation through combinations of recruitment maneuvers, mean airway pressure, and oxygen concentration. The guiding principles were to provide lung protective ventilation by minimizing the size of tidal volumes, and balance the risks and benefits of lung recruitment and distension. Main Results:HFO may provide smaller tidal volumes and more complete lung recruitment than conventional modes. To optimize these features, we recommend use of the maximum pressure-oscillation amplitude coupled with the highest tolerated frequency, targeting a pH of only 7.25–7.35. This will yield a smaller tidal volume than typical HFO settings where frequency is limited to 6 Hz or less and pressure amplitude is submaximal. Lung recruitment can be achieved with the use of recruitment maneuvers, especially during the first several days of HFO. Recruitment may be augmented or sustained with generous mean airway pressures. These may either be chosen from a table of recommended mean airway pressure and oxygen concentration combinations, or individually titrated based on the oxygenation response of each patient. Conclusions:Modification of the goals and tactics of HFO use may better protect against ventilator-associated lung injury. Further clinical trials are needed to compare the effects on patient outcome of the best use of HFO compared to the most protective use of conventional modes in adult acute respiratory distress syndrome.

Noninvasive positive-pressure ventilation in acute respiratory failure outside clinical trials: experience at the Massachusetts General Hospital.

Background: Noninvasive positive-pressure ventilation (NPPV) has been shown to be effective in select patients enrolled in clinical trials. However, few data are available on the use of NPPV as routine standard medical care for patients with respiratory failure outside of controlled trials. Measurements and Main Results: All patients receiving NPPV for a 1-yr period for acute or acute on chronic respiratory failure who did not select do not intubate/resuscitate status were evaluated. Demographic, physiological, and laboratory data were collected for as long as NPPV was provided. Data were recorded on 449 patients. Intubation rate was 18%, 24%, 38%, 40%, and 60%, respectively, for patients with cardiogenic pulmonary edema (n = 97), acute exacerbation of chronic obstructive pulmonary disease (n = 87), non-chronic obstructive pulmonary disease acute hypercapnic respiratory failure (n = 35), postextubation respiratory failure patients (n = 95), and acute hypoxemic respiratory failure (n = 144). The hospital mortality for patients with acute hypoxemic respiratory failure who failed NPPV was 64%. A logistic regression showed that baseline Simplified Acute Physiology Score II (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05–1.10; p <.0001), Glasgow Coma Scale (OR, 0.76; 95% CI, 0.66–0.87; p <.0001), Pao2/Fio2 ratio (OR, 0.98; 95% CI, 0.93–0.99; p = .02), and serum albumin (OR, 0.30; 95% CI, 0.16–0.57; p < .001) were the variables associated with NPPV failure. Conclusion: NPPV as routine standard medical care resulted in the intubation of a similar percentage of patients with respiratory failure due to cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbation as shown in randomized controlled trials but in a higher percent of patients with hypoxemic respiratory failure than reported in these trials. NPPV failure was associated with high hospital mortality for patients with hypoxemic respiratory failure.