Inverse ratio ventilation compared with PEEP in adult respiratory failure

We have compared the cardiorespiratory effects of an inspiratory: expiratory (I:E) ratio of 4:1 with a ratio of 1:2 in 10 adult patients requiring intermittent positive pressure ventilation (IPPV) for acute respiratory insufficiency. Further comparisons were made with IPPV with positive end-expiratory pressure (PEEP) which was adjusted to achieve an equal external end-expiratory volume (EEEV) to that produced by the 4:1 ratio, as determined by respiratory inductive plethysmography, and with an I:E ratio that only changed the EEEV minimally (IRV-min). Percentage pulmonary shunt (Qs/Qt) was reduced equally with PEEP and with the 4:1 I:E ratio but both patterns reduced cardiac output and oxygen delivery. IRV-min also reduced Qs/Qt significantly but had no effect on cardiac output so that oxygen delivery was increased. The dead space to tidal volume ratio (V_D/V_T) during IPPV-4:1 and IRV-min was reduced significantly when compared with that during IPPV-1: 2. The clinical implications of the findings suggest that for some ITU patients, a modest increase in I:E ratio to between 1.1:1 and 1.7:1 may produce better gas exchange without significantly effecting the cardiac output.     

Systemic phospholipase A2 and cachectin levels in adult respiratory distress syndrome and multiple-organ failure.

In this clinical study we have prospectively measured plasma phospholipase A2 (PLA2) activity and tumor necrosis factor (TNF) levels in ventilated intensive care unit (ICU) patients with (n = 9) and without (n = 12) evidence of respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). The median peak TNF concentration in control patients was 40 ng/L (range less than 40-100 ng/L) and in ARDS patients 231 ng/L (range 100-2550 ng/L; p less than 0.001). All of the control patients were discharged alive from the ICU, whereas 6 of 9 ARDS patients died in the ICU. In 6 ARDS patients, it was possible to measure more than 4 consecutive plasma TNF levels. Of these 6 patients, the 3 with persistent elevations in systemic TNF above 230 ng/L succumbed (p less than 0.05, one-tailed). Patients with ARDS also had parallel elevations in plasma PLA2 activity above controls. These elevations were significant for arterial PLA2 activity but not for venous PLA2 activity. Our study suggests that serial measurement of plasma (arterial or venous) TNF levels may have (1) prognostic and (2) etiologic significance in ICU patients with ARDS and MOF.     

The adult respiratory distress syndrome

The adult respiratory distress syndrome (ARDS) is an extreme form of noncardiogenic pulmonary edema associated with alveolar-capillary damage. Clinical features include acute respiratory distress, dyspnea and tachypnea, severe hypoxemia refractory to oxygen therapy, and diffuse bilateral pulmonary infiltrates. Any number of serious disorders can cause ARDS, but the processes leading to the alveolar permeability defect are not understood. Therefore, therapy remains nonspecific and supportive. Treatment includes positive end-expiratory pressure, careful fluid management, steroid therapy, and adequate nutrition. Unfortunately, even with the most sophisticated intensive care, the mortality of ARDS is still greater than 50%.     

Miliary tuberculosis and adult respiratory distress syndrome

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role.     

Care of postoperative patients with adult respiratory distress syndrome

Providing care to the postanesthesia patient requires precise and continual assessment in conjunction with prompt and aggressive intervention. This article discusses the cause, pathology, diagnosis, and management of adult respiratory distress syndrome in the PACU.     

Prevention of the adult respiratory distress syndrome with dipyridamole

Because the formation of platelet thrombi has been incriminated in the development of the adult respiratory distress syndrome (ARDS), we tested the hypothesis that early administration of antiplatelet agents might protect the lungs in patients at risk to develop ARDS after circulatory shock. This double-blinded study included 40 patients treated with either 3 mg/kg . 24 h of dipyridamole or a corresponding dose of placebo after an episode of hemorrhagic, traumatic, or septic shock. Each patient also received 100 mg of aspirin daily. Arterial blood gases and chest x-rays were not significantly different between dipyridamole and placebo groups. Moreover, two patients receiving dipyridamole but none receiving placebo developed ARDS. This pilot study does not support a beneficial effect of dipyridamole in the prevention of ARDS after circulatory shock.     

Dazoxiben in human sepsis and adult respiratory distress syndrome

Levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2, are elevated in human and experimental septic shock. The thromboxane synthetase inhibitor dazoxiben has improved survival and decreased pulmonary hypertension in experimental endotoxemia. A randomized prospective study of 10 patients with the clinical diagnosis of sepsis and early adult respiratory distress syndrome (hypoxemia, radiologic evidence of the syndrome, and intrapulmonary shunt greater than 20%) was performed to test the efficacy of dazoxiben in ameliorating the effects of human sepsis. Five subjects received dazoxiben and five received placebo. Dazoxiben, 100 mg, or placebo was injected intravenously every 4 hours for a maximum of 72 hours. Plasma immunoreactive TxB2 (iTxB2) levels were determined by radioimmunoassay. Before dazoxiben, the plasma iTxB2 level was 752 +/- 261 pg/ml (n = 5) and was reduced within 1 hour to 333 +/- 137 pg/ml. The plasma levels of iTxB2 remained significantly decreased with subsequent doses of dazoxiben and it was 201 +/- 67 pg/ml (n = 4) 60 hours after dosing. In contrast, placebo had no significant effect on plasma iTxB2 levels (n = 5) throughout the entire period of observation. Dazoxiben did not induce any significant changes in pulmonary or systemic vascular resistance, intrapulmonary shunting, clotting studies, or extravascular lung water. One of the five subjects in the placebo group died and two of the five subjects in the dazoxiben group died. We conclude that dazoxiben was safe and effectively lowered plasma iTxB2 levels in patients with sepsis and incipient adult respiratory distress symptom, but did not significantly alter the hemodynamic and pulmonary sequelae of established sepsis.     

Thromboxane and prostacyclin release in adult respiratory distress syndrome

Plasma thromboxane B₂ (TXB₂) and 6-ketoprostaglandin F₁ (6-keto-PGF₁) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (>140 pg/ml plasma) TXB₂ values were found in 52/84 patients. The median values of TXB₂ were: 360 pg/ml in multiple injured, 250 pg/ml in abdominal surgery and 410 pg/ml in acute pancreatitis patients. The median TXB₂ value was 575 pg/ml in patients developing ARDS and 140 pg/ml in those without this complication: this difference was statistically significant (p<0.05). The median values of 6-keto-PGF₁ were 55pg/ml in multiple injured, 25 pg/ml in abdominal surgery and 120 pg/ml in acute pancreatitis patients. The median 6-keto-PGF₁ value was 122 pg/ml in ARDS patients and 25 pg/ml in non-ARDS patients (statistically significant: p<0.05). High TXB₂ and 6-keto-PGF₁ values were particularly related to sepsis in abdominal surgery patients (p<0.05) and in multiple injured patients (p<0.01). No relation could be established between abnormal TXB₂ or 6-keto-PGF₁ values and death. High TXB₂ values often persisted for several days and were observed particularly at the time ARDS diagnostic criteria were fulfilled. An imbalance between TXB₂ and 6-keto-PGF₁ was observed: 6-keto-PGF₁ values were always lower than TXB₂ values and did not persist for more than 24 h except in four cases. Our data demonstrate a significant production of prostanoids in ARDS patients particularly in sepsis and indicate a disturbance in balance of the prostacyclin/thromboxane axis.     

Prevention of adult respiratory distress syndrome with plasminogen activator in pigs

Death from traumatic shock has been associated with loss of blood externally or internally. However, many patients die after trauma, even though blood volume restoration is adequate. Death is often due to pulmonary failure (adult respiratory distress syndrome [ARDS]). Death and ARDS have been associated with disseminated intravascular coagulation (DIC) and microclots in the lungs. Dissolution of the microclots after trauma can be achieved by activation of endogenous plasmin. Nine pigs were anesthetized for 48 h. Trauma was administered by 60 standard blows to each thigh resulting in a bruise of muscle but no skin, bone, or major vessel injury. Nutrition and respiration were maintained at normal levels. All nine pigs died with severe lung pathology and low PaO2. Ten other traumatized pigs were treated with a plasminogen activator iv 4 h after trauma. Five of these were treated with tissue plasminogen activator (tPA) and five with urokinase. All treated pigs survived 48 h and maintained a normal PaO2. Autopsy showed minimal lung pathology.     

Effect of end-stage liver failure on the incidence and resolution of the adult respiratory distress syndrome

Multiple systems organ failure adversely affects outcome in the adult respiratory distress syndrome (ARDS). However, no clinical studies of the influence of preexisting single extrapulmonary organ dysfunction on the incidence and resolution of ARDS have been reported. Hepatic reticuloendothelial system (RES) and hepatic parenchymal cell uptake and detoxification of proinflammatory substances are major elements of systemic host defense and may, accordingly, be important pulmonary defense mechanisms. To better define the effects of liver-lung interactions on the resolution of acute lung injury with preexisting extreme hepatic dysfunction, we retrospectively analyzed the incidence, risk factors, and clinical characteristics of ARDS in 29 patients with end-stage liver failure (ESLF) who required intensive care while awaiting a liver transplantation. We compared data from these patients with those from a concurrent group of 44 intensive care patients without ESLF, and contrasted our findings with recent clinical studies of ARDS predisposition and outcome. ARDS occurred in 23 of 29 patients (79%) with ESLF; sepsis was the most common predisposing risk factor (18 of 29 patients, 62%). ARDS developed in 3 of 44 patients (6.8%) without ESLF (odds ratio comparison with ESLF patients, 42.9, P < .001). Once initiated, regardless of etiology and subsequent ventilatory support, ARDS was uniformly irreversible in all 23 ESLF patients. These findings identify a growing population of critically ill patients at increased risk for nonresolving severe acute lung injury despite current methods of intensive care. We conclude that compromise of systemic and pulmonary defense by impaired hepatic RES performance and hepatocyte function may both predispose to ARDS and critically modulate its resolution.     

Hemofiltration in severe septic adult respiratory distress syndrome associated with varicella

One case of severe varicella pneumonia with high microvascular permeability pulmonary edema and signs of multiple system organ disfunction was successfully treated by means of hemofiltration. The patient was discharged from the Intensive Care Unit 6 days after admission. Peptides showing molecular weight ranging between 600 (prostaglandins) and 4000 (B-endorphin) daltons were cleared from blood at the same rate as urea. Hemofiltration appears to be a valuable tool for treating septic ARDS.     

Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome

Oxygen metabolites have been implicated in the pathogenesis of various types of acute tissue injury. One biologic source of oxygen metabolites is the reaction catalyzed by the enzyme xanthine oxidase. Because we previously demonstrated that the substrates for xanthine oxidase (hypoxanthine and xanthine) are elevated in the plasma of critically ill patients, we questioned whether the enzyme itself might also be present. We therefore measured hypoxanthine concentration and xanthine oxidase activity in the plasma of 15 patients with ARDS and in 13 non-ARDS critically ill patients. Plasma xanthine oxidase activity in our ARDS group (1,514 ± 975 mlU/L, mean ± SE) was higher than that seen in the non-ARDS group (17 ± 4 mlU/L, P .05). Plasma hypoxanthine was elevated in both groups, and there was no difference between the ARDS and non-ARDS groups (22.0 ± 9.2 μmol/L and 11.8 ± 4.3 μmol/L, respectively). The presence of both circulating xanthine oxidase and its substrate demonstrates the potential for intravascular oxygen metabolite production. These toxic products may then cause tissue injury in ARDS.     

Combined high-frequency ventilation in children with severe adult respiratory distress syndrome

Six children conventionally ventilated for acute pulmonary parenchymal failure developed severe hypoxemia (mean PaO₂ 48±7 mmHg at an FiO₂ of 0.95±0.08) persisting for more than 6 h despite a progressive increase in positive end expiratory pressure (PEEP) to 14.7±1.5 cmH₂O. Combined high-frequency jet ventilation (HFJV, mean rate 225 b/min superimposed on small tidal volume conventional ventilation) resulted in a sustained increase in PaO₂ to 93±21 mmHg,p<0.05 while peak inspiratory pressure decreased from 47±8 to 35±6 cmH₂O and positive end expiratory pressure could be reduced to 5.8±4.5 cmH₂O,p<0.05 and FiO₂ to 0.88±0.10. This improvement occurred without new barotrauma nor deleterious effects on hemodynamic function or diuresis. After a mean of 62 h of combined HFJV, persistant improvement in gas exchange allowed us to resume conventional mechanical ventilation at lower airway pressures in 4 children who continued to improve and survived. The 2 other children maintained satisfactory gas exchange on combined HFJV, but ultimately died from multiple organ failure. We conclude that combined HFJV might prove helpful to relieve profound hypoxemia and possibly decrease the risk of barotrauma in children with catastrophic pulmonary failure.This study was presented in part at the Annual Meeting of the Swiss Society of Intensive Care Medicine, Basel, Switzerland, October 1989.     

Immunoreactive trypsin in the adult respiratory distress syndrome

With the purpose of studying the role of proteinases in the development of ARDS, plasma levels of immunoreactive trypsin (IRT) and amylase were measured in 43 intensive care patients at risk of developing ARDS (22 polytrauma, seven abdominal surgery, four burns, two DIC and eight pancreatitis). Twenty four of these 43 patients developed ARDS and 31 presented abnormal IRT values (above 70 g/L). Twenty-one of these 31 patients had ARDS; a significant correlation thus appeared between ARDS and abnormal IRT values. In nine patients, IRT values were higher than 800 g/L and remained high for 3 to 4 days. A statistically significant correlation also appeared between abnormal IRT and septic phenomena: 20 patients with high IRT values presented septic problems. When IRT values were high, amylase values were often also abnormal: 12 of 23 patients with high IRT had abnormal amylase levels (the eight patients with documented pancreatitis were excluded); no other clinical signs or symptoms of pancreatitis were present in these patients. IRT could be one of the mediators of ARDS in septic patients. It is not clear that the pancreas is the origin of IRT in all cases.     

Pulmonary microthrombosis in severe adult respiratory distress syndrome

Pulmonary microvascular occlusive disease has been investigated using balloon occlusive pulmonary angiography in 31 patients with severe adult respiratory distress syndrome (ARDS) of different origins (14 patients with pneumonia, nine with multiple injury, eight with sepsis). Multiple pulmonary artery filling defects (PAFD) were detected in 13 (42%) patients, with a seven (78%) in nine incidence among those with posttraumatic ARDS. The presence of PAFD did not correlate with the severity of the respiratory failure, with the pulmonary hemodynamic alterations (pulmonary hypertension and increased vascular resistance), or with the final outcome (mortality rate was 54% among patients with PAFD and 61% among those with normal angiograms). These findings suggest that widespread pulmonary microthrombosis is a common event in patients with polytrauma and respiratory failure, with an important pathophysiologic role in the onset of posttraumatic ARDS.