Positive end-expiratory pressure, prone positioning, and activated protein C: a critical review of meta-analyses

The results of meta-analyses on the effectiveness of high positive end-expiratory pressure (PEEP) and prone positioning in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are not consistent. In addition, the meta-analyses on the activated protein C in patients with sepsis combine trials with discordant results. Therefore, the aim of this paper was to give a critical review of these meta-analyses. All relevant meta-analyses were identified by a computerized search of PubMed using combinations of the following terms: acute lung injury, acute respiratory distress syndrome, positive end-expiratory pressure, mechanical ventilation, prone position, drotrecogin, activated protein C, sepsis, and septic patients. A high level of PEEP and prone ventilation was shown to reduce the mortality in patients with severe acute hypoxemic respiratory failure. Although the evidence for the efficacy of activated protein C is not conclusive, it should be considered in patients that are at a high risk for death without any contraindications related to bleeding risk. Meta-analysis models can be very useful for clinical decisions if they include all of the similar papers on a medical topic and are correct from the methodological point of view; however, these results must be checked by a careful and well-informed reader.     

Prone Position for the Treatment of Acute Respiratory Distress Syndrome: A Review of Current Literature

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have high incidence and mortality rates. Most of the recently introduced treatments have failed to improve the prognosis of patients with ALI or ARDS or to reduce mortality. Several studies have shown improved oxygenation in the prone position during mechanical ventilation in patients with ARDS. However, current evidence strongly suggests that placing ARDS patients in prone position does not improve survival or reduce the duration of mechanical ventilation. Therefore, though in clinical practice this position may improve refractory hypoxemia in patients with ARDS, there is no evidence to support its systematic use.     

Optimal ventilator settings in acute lung injury and acute respiratory distress syndrome

Despite recent advances in intensive care medicine, acute lung injury and its more severe form, acute respiratory distress syndrome pose major therapeutic problems. While mechanical ventilation is integral to the care of these patients, its adverse consequences including ventilator-induced lung injury are determinants of disease progression and prognosis. Among several important ventilator parameters, the use of low tidal volumes is probably the most important feature of lung-protective mechanical ventilation. Intensivists should be trained to recognize acute lung injury and acute respiratory distress syndrome and encouraged to use low-tidal-volume ventilation in clinical practice. Alternative modes of ventilation such as high-frequency ventilation and prone position should be reserved for selected patients in whom conventional lung-protective ventilation strategies have failed.     

Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome

INTRODUCTION: Prone ventilation improves oxygenation in selected patients with acute respiratory distress syndrome (ARDS). However, prone positioning of critically ill patients with multiple invasive lines and tubes is potentially dangerous. Trauma patients, in particular, may require special consideration because of skeletal fixation devices or prior operative procedures. Our objective was to critically evaluate our experience with prone positioning in patients with severe postinjury ARDS. METHODS: Injured patients admitted to our Level I trauma center who developed ARDS were prospectively identified. Serial lung injury severity and pulmonary mechanical data, as well as complications of prone ventilation were recorded. RESULTS: During the 12-month period ending August of 1998, nine patients with postinjury ARDS were treated with prone ventilation because of hypoxemia refractory to other ventilatory strategies. All patients suffered blunt trauma. Their mean age was 29 +/- 4.5 years; seven patients were men. The average Injury Severity Score was 26 +/- 5; and, at the time of prone positioning, the mean Lung Injury Score was 3.5. The mean PaO2/FIO2 ratio increased from 75 +/- 7 to 147 +/- 27 with prone ventilation (p < 0.05, paired t test); and in six patients, the FIO2 could be decreased. Four major complications occurred (44%). One patient experienced a midline abdominal wound dehiscence. Severe facial or upper chest wall pressure necrosis developed in two patients, despite extensive padding and careful attention to skin care. The fourth patient sustained a cardiac arrest immediately after prone positioning. CONCLUSION: Prone ventilation in postinjury patients with ARDS may improve oxygenation but has the potential for significant complications. Careful consideration is required before prone positioning in this subset of patients.     

Combined effects of prone positioning and airway pressure release ventilation on gas exchange in patients with acute lung injury

BACKGROUND: Prone positioning has been shown to improve oxygenation in 60-70% of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Another way to improve matching of ventilation to perfusion is the use of partial ventilatory support. Preserving spontaneous breathing during mechanical ventilation has been shown to improve oxygenation in comparison with controlled mechanical ventilation. However, no randomized studies are available exploring the effects of preserved spontaneous breathing on gas exchange in combination with prone positioning. Our aim was to determine whether the response of oxygenation to the prone position differs between pressure-controlled synchronized intermittent mandatory ventilation with pressure support (SIMV-PC/PS) and airway pressure release ventilation with unsupported spontaneous breathing (APRV). METHODS: We undertook a prospective randomized intervention study in a medical-surgical adult intensive care unit of a university hospital. Of 45, 33 ALI patients (acute lung injury) within 72 h after initiation of mechanical ventilation, and in whom the prone position was applied according to a predefined strategy, were included in the study. After initial stabilization the patients were randomized to receive either SIMV-PC/PS or APRV with predefined general ventilatory goals (PEEP, tidal volume, inspiratory pressure and PaCO2-level). The protocol for prone positioning was the same for both treatment arms. Prone positioning was triggered by finding a PaO2/FiO2-ratio below 200 mmHg evaluated twice per day. The duration of each prone episode was 6 h. RESULTS: The first two episodes of prone positioning were analyzed. Gas exchange was measured before and at the end of prone positioning. Of the 45 patients enrolled, 33 were turned prone once and 28 twice. No significant differences were detected in baseline characteristics. Changes in oxygenation were analyzed in response to the first and second prone episodes 5 h and 24 h after randomization and initiation of SIMV-PC/PS or APRV respectively. Before the first prone episode the PaO2/FiO2-ratio was significantly better (P = 0.02) in the APRV-group (median; interquartile range) (162; 108-192 mmHg) than in the SIMV-PC/PS-group (123; 78-154 mmHg). The response in oxygenation to the first prone episode was similar in both groups: PaO2/FiO2-ratio increased 39.5; 17.75-77.5 mmHg in the SIMV-PC/PS-group and 75.0; 9.0-125.0 mmHg in the APRV-group (P = 0.49). Before the second prone episode, the PaO2/FiO2-ratio was comparable (SIMV-PC/PS 130.5; 61.0-161.0 mmHg vs. APRV 134; 98.3-175.0 mmHg). Improvement in oxygenation was significantly (P = 0.02) greater in the APRV group (82; 37.0-141.0 mmHg) than in the SIMV-PC/PS group (50; 24.0-68.8 mmHg) during the second prone episode. General ventilatory and hemodynamic variables and use of sedatives were similar in both groups during the study. CONCLUSIONS: APRV during prone positioning is feasible in the treatment of ALI patients. APRV after 24 h appears to enhance improvement in oxygenation in response to prone positioning.     

Lung protective ventilation - supportive and adjunctive therapies in acute lung injury

Various supportive and adjunctive therapies to conventional mechanical ventilation have been evaluated in patients with acute lung injury and acute respiratory distress syndrome (e.g. nitric oxide, prone position, surfactant, glucocorticoids). Although some investigations have shown promising improvements in oxygenation and physiological variables, large randomized trials of adjunctive and supportive therapies showed no impact on survival.     

急性呼吸窘迫综合征患者清醒俯卧位通气体验的质性研究

目的 深入探索急性呼吸窘迫综合征患者行清醒俯卧位通气治疗的体验。方法 采用描述性质性研究,于2023年4-6月对17例行俯卧位通气的急性呼吸窘迫综合征患者进行半结构化访谈,采用内容分析法分析资料。结果 通过对质性数据的总结和分析,共提炼出4个主题,包括治疗动机和期望、患者体验和感受、俯卧位依从性的促进因素、俯卧位依从性的障碍因素。结论 急性呼吸窘迫综合征患者清醒俯卧位通气的体验受一系列因素的影响。对于需行清醒俯卧位通气的患者,提高患者舒适度、增强患者治疗动机和期望、调动家庭社会支持系统以及支持患者的自我管理努力将有助于提高患者的依从性。     

Clinical impact of recruitment maneuvers in patients with acute respiratory distress syndrome

In patients with acute respiratory distress syndrome (ARDS), recruitment maneuvers have been proposed as an adjunct to mechanical ventilation to open up atelectasis and to keep these alveoli open by the application of adequate high levels of positive end-expiratory pressure (PEEP). Though several studies reported that the responsiveness to recruitment maneuvers resulted in a marked improvement of oxygenation with a concomitant decrease in airway pressure and/or inspiratory fraction of oxygen, the performance of recruitment maneuvers still remains a matter of dispute, especially in patients ventilated with a lung protective ventilation strategy. In this review we discuss the pathophysiological background, factors affecting the responsiveness to recruitment maneuvers and their clinical impact in the light of recently published studies. Successful recruitment depends on several factors like the applied recruitment pressure, the level of PEEP set before and after the recruitment maneuver, the stage and the underlying disease of the ARDS, chest wall mechanics and the transpulmonary pressure as well as the positioning of the patient. Regarding the current literature, recruitment maneuvers may be considered as a rescue therapy in the early stage of severe hypoxemic lung failure, if a lung protective ventilation strategy and other additive adjuncts like prone positioning or the application of inhaled vasodilators failed to induce adequate gas exchange.     

Prone positioning improves oxygenation in post-traumatic lung injury--a prospective randomized trial

BACKGROUND: In a prospective randomized trial the effect of prone positioning on the duration of mechanical ventilation was evaluated in multiple trauma patients and was compared with patients ventilated in supine position. METHOD: Multiple trauma patients of the intensive care units of two university hospitals were considered eligible if they met the criteria for acute lung injury or the acute respiratory distress syndrome. Patients in the prone group (N = 21) were kept prone for at least eight hours and a maximum of 23 hours per day. Prone positioning was continued until a PaO2:FiO2 ratio of more than 300 was present in prone as well as supine position over a period of 48 hours. Patients in the supine group (N = 19) were positioned according to standard care guidelines. RESULTS: The duration of ventilatory support did not differ significantly (30 +/- 17 days in the prone group and 33 +/- 23 days in the supine group). Worst case analysis (death and deterioration of gas exchange) displayed ventilatory support for 41 +/- 29 days in the prone group and 61 +/- 35 days in the supine group (p = 0.06). The PaO2:FiO2 ratio increased significantly more in the prone group in the first four days (p = 0.03). The prevalence of Acute Respiratory Distress Syndrome (ARDS) following acute lung injury (p = 0.03) and the prevalence of pneumonia (p = 0.048) were reduced also. One patient in the prone and three patients in the supine group died due to multi organ failure (p = 0.27). CONCLUSIONS: Intermittent prone positioning was not able to reduce the duration of mechanical ventilation in this limited number of patients. However the oxygenation improved significantly over the first four days of treatment, and the prevalence of ARDS and pneumonia were reduced.     

Mechanical ventilation in the management of acute respiratory distress syndrome

The occurrence of acute respiratory distress syndrome (ARDS), is now common in intensive care units throughout the world. The diagnosis of ARDS is based on a definition that includes bilateral pulmonary infiltrates on chest radiographs, impaired oxygenation, and the absence of clinical evidence of elevated left atrial pressure. ARDS is the clinical result of a group of diverse processes, which range from physical or chemical injury, to extensive activation of innate inflammatory response. All these processes damage the integrity of the alveolar-capillary barrier causing increased alveolar-capillary permeability and an influx of protein-rich fluid into the alveolar space. This alveolar flooding results in hypoxemia, inactivated surfactant, intrapulmonary shunt, and impaired alveolar ventilation. The treatment of acute respiratory distress syndrome is largely supportive in nature, keeping patients alive while allowing their lungs to heal, and minimizing further pulmonary insult. In 1994 the National Heart, Lung, and Blood Institute (NHLBI) established the ARDS Network for the conduct of clinical trials. This is a network, supported by the National Institutes of Health, that provided the infrastructure for well-designed, multicenter, randomized trials of therapies for ARDS. The first study from this group in 2001 produced landmark data demonstrating mortality improvements in ARDS with particular mechanical ventilation strategies. Specifically, low tidal volume mechanical ventilation was demonstrated to reduce mortality by 22%. Other strategies such as high positive end expiratory pressure and prone positioning have not been shown to reduce mortality. Clinicians who are involved in the care of patients with ARDS should have a basic understanding of mechanical ventilation and the evidence guiding the mechanical ventilation strategies of these patients. Until further evidence is published, providers should adopt the use of a volume and pressure limited approach to mechanical ventilation.     

Prone positioning and inhaled nitric oxide: synergistic therapies for acute respiratory distress syndrome

BACKGROUND: Inhaled nitric oxide (INO) and prone positioning have both been advocated as methods to improve oxygenation in patients with acute respiratory distress syndrome (ARDS). This study was designed to evaluate the relative contributions of INO and prone positioning alone and in combination on gas exchange in trauma patients with ARDS. METHODS: Sixteen patients meeting the consensus definition of ARDS were studied. Patients received mechanical ventilation in the supine position, mechanical ventilation plus INO at 1 part per million in the supine position, mechanical ventilation in the PP, and mechanical ventilation in the prone positioning plus INO at 1 part per million. A stabilization period of 1 hour was allowed at each condition. After stabilization,hemodynamic and gas exchange variables were measured. RESULTS: INO and prone positioning both increased PaO2/FIO2 compared with ventilation in the supine position. PaO2/FIO2 increased by 14% during use of INO, and 10 of 16 patients (62%) responded to INO in the supine position. PaO2/FIO2 increased by 33%, and 14 of 16 patients (87.5%) responded to the prone position.The combination of INO and prone positioning resulted in an improvement in PaO2/FIO2 in 15 of 16 patients(94%), with a mean increase in PaO2/FIO2 of 59%. Pulmonary vascular resistance was reduced during use of INO, with a greater reduction in pulmonary vascular resistance seen with INO plus prone positioning (175 +/- 36 dynes x s/cm5 vs. 134 +/- 28 dynes x s/cm5) compared with INO in the supine position (164 +/- 48 dynes x s/cm5 vs.138 +/- 44 dynes x s/cm5). There were no significant hemodynamic effects of INO or prone positioning and no complications were seen during this relative short duration of study. CONCLUSIONS: INO and prone positioning can contribute to improved oxygenation in patients with ARDS. The two therapies in combination are synergistic and may be important adjuncts to mechanical ventilation in the ARDS patient with refractory hypoxemia.     

Trends in and perspectives on extracorporeal membrane oxygenation for severe adult respiratory failure

Various approaches such as ventilator management involving lung-protective ventilation, corticosteroids, prone positioning, and nitric oxide have failed to maintain sufficient lung oxygenation or appropriate ventilation competence in very severe acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) has been aggressively introduced for such patients, although in only a few institutions. The clinical usefulness of ECMO in a large-scale multicenter study (CESAR trial, 2009) and continued development/improvement of ECMO devices have facilitated performance of ECMO, with further increase in the number of institutions adopting ECMO therapy. Clinical usefulness of ECMO was documented in many cases of severe ARDS secondary to influenza A (H1N1) 2009 infection. ECMO requires establishment of an appropriate management system to minimize fatal complications (e.g., hemorrhage), which requires a multidisciplinary team. This, in combination with a new technique, interventional lung assist, will further extend the indications for ECMO. ECMO can be expected to gain importance as a respiratory support technique.     

Mechanical ventilation in acute respiratory distress syndrome

The acute respiratory distress syndrome occurs commonly in critical care. There is an increasing volume of clinical and experimental evidence that poor ventilatory technique that is injurious to the lungs can propagate the systemic inflammatory response and adversely affect mortality. Many ventilatory techniques have been hypothesized to 'protect' the lungs during mechanical ventilation, including tidal volume limitation, high positive end-expiratory pressure, pressure-controlled inverse ratio ventilation, and prone positioning. Experimental techniques include liquid ventilation, surfactant administration and extracorporeal gas exchange. Despite excellent rationale for their use, few techniques, apart from tidal volume limitation, have been shown to improve survival in randomized controlled trials.     

Protektive Beatmungstherapie

General anesthesia and mechanical ventilation affect gas exchange, ventilation and pulmonary perfusion and there is an increasing body of evidence that mechanical ventilation itself promotes lung injury. Lung protective mechanical ventilation in patients suffering from acute lung injury or acute respiratory distress syndrome by means of reduced tidal volumes and limited plateau pressures has been shown to result in reduction of systemic inflammatory mediators, increased ventilator-free days and reduction in mortality. Experimental studies suggest that mechanical ventilation of uninjured lungs may also induce lung damage; however, the clinical relevance remains unknown. Human prospective studies comparing mechanical ventilation strategies during general anesthesia have shown inconsistent results with respect to inflammatory mediators. There is a lack of clinical evidence that lung protective ventilation strategies as used in patients with lung injury may improve clinical outcome of patients with uninjured lungs. The question of which ventilatory strategy will best protect normal human lungs remains unanswered.     

Extracorporeal membrane oxygenation in acute respiratory distress syndrome after a liver transplant

Extracorporeal membrane oxygenation (ECMO) is used in the treatment of severe respiratory failure that is potentially reversible. This mode of therapy reduces ventilator-associated lung injury. Although ECMO is costly and not free of complications, its early application by experienced multidisciplinary teams can improve survival. We report a case of acute respiratory distress syndrome in a patient who had received a liver transplant. Respiratory failure was unresponsive to conventional treatment and the patient required ECMO until recovery.     

Pathophysiology and treatment of postoperative acute respiratory disturbance

One major concern after surgery is postoperative pulmonary complications such as atelectasis, aspiration, pneumonia, and respiratory failure. Progress in preoperative and postoperative rehabilitation, in systemic management including respiratory management, and progress in understanding the pathophysiology of acute respiratory failure have improved prevention and the outcome of treatment. However, some conditions remain very difficult to treat, like respiratory failure accompanied by infection or multiple organ failure. In the 1960s, the concept of acute respiratory distress syndrome or adult respiratory distress syndrome was postulated. Tremendous amounts of basic and clinical research have been done to clarify the pathophysiology of and to establish treatment modalities for acute respiratory failure. Our understanding of acute respiratory failure has progressed from the role of microembolism syndrome to cellular components such as neutrophils and platelets and then to humoral factors such as endotoxins, complement factors, and numerous cytokines. In this article, the pathophysiology of acute lung injury and its diagnostic criteria, treatment modalities such as respirator management to protect lung tissue from barotrama and volutrauma by yielding hypercapnea (permissive hypercapnea), drug therapy with neutrophil elastase inhibitor, mechanical support using extracorporeal membrane oxygenation, liquid ventilation, continuous hemodiafiltration, and endotoxin elimination columns are discussed. Early diagnosis and early treatment are mandatory to improve survival in patients with acute respiratory failure, although we have not yet fully understood the pathophysiology of this disease entity sufficiently.     

Prone Positioning as a Bridge to Recovery From Refractory Hypoxemia After Oversized Lung Transplant

BackgroundSize matching is an important challenge in lung transplantation. Although the survival rate after lung transplantation with an oversized allograft was improved, it is associated with substantial immediate postoperative morbidity and mortality. Prone positioning is a rescue therapy showing improved outcomes in acute respiratory distress syndrome. We present a case of immediate postoperative refractory hypoxemia after oversized lung transplantation treated by prone positioning.MethodsA 62-year-old man was transferred to our hospital by our extracorporeal membrane oxygenation (ECMO) transport team because of acute exacerbation of idiopathic pulmonary fibrosis. He underwent bilateral lung transplantation through bilateral anterior thoracotomy. For size matching between donor and recipient, multiple wedge resection and lingular segmentectomy were performed, but an oversized lung was implanted. On the immediate postoperative day, chest radiography revealed haziness in the left lower quadrant and the patient had an increased O₂ requirement; he could not be weaned from venovenous (VV) ECMO. Chest computed tomography revealed left lower lobar atelectasis and primary graft dysfunction. To revert the atelectatic portion, improve ventilation/perfusion mismatch, and avoid high ventilation pressure, we performed the recruitment maneuver. Despite this, his blood gas profile did not improve. Therefore, we applied prone positioning with VV ECMO. After conversion to the prone positioning, the hypoxia corrected and the tidal volume increased. After 20 hours, he was changed to the supine position. Thereafter, arterial blood gas analyses were stable and he could be weaned from ECMO. He was discharged on postoperative day 57 and maintained good respiratory function.ConclusionsThis case demonstrated the safety and feasibility of prone positioning during the immediate postoperative period after lung transplant by bilateral anterior thoracotomy. Prone positioning successfully reversed postoperative atelectasis and improved primary graft dysfunction after oversized lung transplant.     

Protective ventilation strategy in the acute respiratory distress syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) contribute to progressive hypoxemia in critically ill patients. It has been proved that conventional mechanical ventilation with physiological respiratory volume contributes to further lung damage. In this respect, application of protective ventilatory strategy--pulmonary ventilation with limited volume and pressure can avoid mentioned consequences. The aim of this paper is to discuss mechanims by which elements contained in protective mechanical ventilation of patients with ALI/ARDS prevent further progrssive lung injury, to argue the effects of positive end--expiratory pressure and present insturctions for its application.     

Immediate effects of positive end-expiratory pressure and low and high tidal volume ventilation upon gas exchange and compliance in patients with acute lung injury.

BACKGROUND: Protective ventilation, in general, includes low tidal volume ventilation and maintaining end-inspiratory plateau pressures less than 35 cmH2O. Recent clinical studies have determined that such an approach results in improved survival in patients with moderate to severe acute lung injury and acute respiratory distress syndrome. However, experimental evidence suggests that repeated end-expiratory collapse and reexpansion contributes to ventilator-induced lung injury. We sought to determine the immediate effects of specific tidal volume-PEEP combinations upon oxygenation and static compliance in patients with moderate to severe acute lung injury. METHODS: Fourteen patients were prospectively studied and were treated with each of 10 tidal volume-PEEP combinations, applied in random order. After 5 minutes at each tidal volume-PEEP combination, PaO2/FIO2 and static compliance were recorded. Comparisons were made between low and high tidal volume ventilation as well as across five PEEP levels. RESULTS: At both low (6 mL/kg) and high (10 mL/kg) tidal volume ventilation, PaO2/FIO2 increased with increasing PEEP, up to 20 cmH2O. Similar changes in static compliance were not evident. Static compliance was highest at PEEP of 10 and 15 cmH2O, regardless of tidal volume. With PEEP set at 5 cmH2O, static compliance was significantly lower with 6 mL/kg than with 10 mL/kg tidal volumes. Overall, static compliance was lowest for both tidal volume conditions with PEEP set at 25 cmH2O. CONCLUSION: Low tidal volume ventilation with PEEP set at 5 cmH2O results in poor oxygenation and compliance in patients with moderate to severe acute lung injury. Similarly, PEEP set at 25 cmH2O did not improve oxygenation or compliance.