Effects of prone position on alveolar recruitment and oxygenation in acute lung injury

Objective: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure.¶Design: Prospective physiologic study.¶Setting: Medical ICU two in a university hospital.¶Patients: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated.¶Measurements and results: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (ΔFRC). The recruited alveolar volume was computed as the ΔFRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO₂/FIO₂ ratio improved from SP1 to PP (136 ± 17 vs 204 ± 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 ± 0.99 cmH₂O/l in SP1 to 6.26 ± 0.54 cmH₂O/l in PP (p < 0.05) without any correlation to the change in oxygenation.¶Conclusions: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.     

Application of a computerised method to measure static pressure volume curve in acute respiratory distress syndrome

Objective: To assess the safety and the bedside feasibility of a new computerised method to record the static pressure-volume curves (Pst/V) of the respiratory system.¶Design: The Pst/V curves were recorded in 13 medical patients with the acute respiratory distress syndrome (ARDS). During the Pst/V curve tracing the following parameters were recorded: time required for the recording and the automatic analysis of the Pst/V curve and modifications in electrocardiograms, blood pressure, and arterial oxygen satmation (SaO₂).¶Setting: The study was performed in the intensive care unit of the University of Naples “Federico II”.¶Results: No statistically significant modifications in heart rate (HR, b min^–1), blood pressure (BP, mmHg), and SaO₂ were observed between conditions at baseline (HR 97.2 ± 17.7; BP 65.4 ± 9.3; SaO₂ 93.6 ± 2.0), during the recording (HR 99.8 ± 19.5; BP 66.2 ± 11.6; SaO₂ 93.7 ± 2.4), and 2 min after the procedure (HR 98.2 ± 17.8; BP 65.2 ± 11.7; SaO₂ 93.7 ± 1.9). The Pst/V curves were recorded in 8.38 ± 1.19 min and fully analysed in 2.69 ± 0.85 min. Mean value of static compliance was 41.1 ± 12.7 ml cmH₂O^–1. A lower inflection point was found in ten patients (mean value 9.2 ± 1.9 cmH₂O).¶Conclusions: In ARDS patients, the present new computerised method gave valuable data to ordinary intensivists and was shown to be safe, easy, and fast.     

ARDS in patients with thermal injury

Objective: To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population.¶Design: Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions.¶Setting: Regional, tertiary referral, adult burn unit in a university teaching hospital.¶Patients and participants: Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995.¶Interventions: None.¶Measurements and results: Of 469 consecutive admissions, 126 (26.9 %) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 ± 5.2 and 8.2 ± 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2 % developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2 %) in those with ARDS compared to those without (p = 0.27).¶Conclusions: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.     

Association of PEEP with two different inflation volumes in ARDS patients: effects on passive lung deflation and alveolar recruitment

Objective: To assess the effects of the association of positive end-expiratory pressure (PEEP) with different inflation volumes (V_T's) on passive lung deflation and alveolar recruitment in ARDS patients.¶Design: Clinical study using PEEP with two different V_T's and analyzing whether passive lung deflation and alveolar recruitment (Vrec) depend on end-inspired (EILV) or end-expired (EELV) lung volume in mechanically ventilated ARDS patients.¶Setting: Medical intensive care unit in a university hospital.¶Patients and participants: Six mechanically ventilated consecutive supine patients with ARDS.¶Interventions: Time-course of thoracic volume decay during passive expiration and Vrec were investigated in six ARDS patients ventilated on PEEP with baseline V_T (V_T,b) and 0.5V_T (0.5V_T,b), and on zero PEEP (ZEEP) with V_T,b. Time constants of the fast (τ ₁) and slow (τ ₂) emptying compartments, as well as resistances and elastances were also determined.¶Measurements and results: (a) the bi-exponential model best fitted the volume decay in all instances. The fast compartment was responsible for 84 ± 7 (0.5V_T,b) and 86 ± 5 % (V_T,b) on PEEP vs 81 ± 6 % (V_T,b) on ZEEP (P:ns) of the exhaled V_T, with τ ₁ of 0.50 ± 0.13 and 0.58 ± 0.17 s vs 0.35 ± 0.11 s, respectively; (b) only τ ₁ for V_T,b on PEEP differed significantly (P < 0.02) from the one on ZEEP, suggesting a slower initial emptying; (c) for the same PEEP, Vrec was higher with a higher volume (V_T,b) than at a lesser one (0.5V_T,b), reflecting the higher V_T.¶Conclusions: In mechanically ventilated ARDS patients: (a) the behavior of airway resistance seems to depend on the degree of the prevailing lung distension; (b) alveolar recruitment appears to be more important when higher tidal volumes are used during mechanical ventilation on PEEP; (c) PEEP changes the mechanical properties of the respiratory system fast-emptying compartment.     

俯卧位通气加肺复张对急性呼吸窘迫综合征的作用

目的 评价俯卧位通气(PPV)联合肺复张(RM)对急性呼吸窘迫综合征(ARDS)犬的肺保护作用及机制.方法 经股静脉快速注入油酸建立犬ARDS模型,容积控制通气,在小潮气量(VT,10 ml/kg)+高呼气末正压(PEEP,16 cm H2O,1 cm H2O=0.098 kPa)通气基础上,按随机数字表法分为仰卧位组、俯卧位组、仰卧+RM组、俯卧+RM组,每组6只.测定通气后0.5、2和4 h血清细胞因子.4 h后经股动脉放血处死动物,开胸取肺;取左肺组织制备匀浆,测定细胞因子;取右肺测定湿/干重(W/D)比值及制备病理切片,行病理评分.结果 ①通气4 h时仰卧+RM组血清白细胞介素-8(IL-8)浓度明显高于其他3组(P均<0.05),且仰卧+RM组血清肿瘤坏死因子-α(TNF-α)浓度明显高于俯卧位组及俯卧+RM组(P均<0.05).②俯卧位组及俯卧+RM组背侧肺组织匀浆中IL-8浓度明显低于仰卧位组(P均<0.05),TNF-α浓度明显低于仰卧+RM组(P均<0.05).③俯卧位组、俯卧+RM组右肺W/D比值明显低于仰卧位组及仰卧+RM组(P均<0.05).④俯卧位组及俯卧+RM组背侧病理评分显著低于仰卧位组及仰卧+RM组(P均<0.05).结论 在犬ARDS模型中,予以小VT+PEEP的肺保护性通气时,在俯卧位实施RM可以减轻肺损伤.     

Influence of abdominal obesity on multiorgan dysfunction and mortality in acute respiratory distress syndrome patients treated with prone positioning

Purpose

Obesity is a worldwide pandemic, and obese patients face an increased risk of developing acute respiratory distress syndrome (ARDS). Prone positioning (PP) is a frequently used intervention in the treatment of ARDS. There are no data describing the impact of PP on morbidity and mortality in abdominally obese patients. We report our observations in abdominally obese ARDS patients treated with PP.

Materials and methods

Patients with ARDS (n = 82) were retrospectively divided into 2 groups characterized by presence (n = 41) or absence (n = 41) of abdominal obesity as defined by a sagittal abdominal diameter of 26 cm or more.

Results

There was no difference in cumulative time abdominally obese patients were placed in prone position from admission to day 7 (41.0 hours [interquartile range, 50.5 hours] vs 39.5 hours [interquartile range, 61.5 hours]; P = .65) or in overall intensive care unit mortality (34% vs 34%; P = 1). However, abdominally obese patients developed renal failure (83% vs 35%; P < .001) and hypoxic hepatitis (22% vs 2%; P = .015) more frequently. A significant interaction effect between abdominal obesity and prone position with respect to mortality risk (likelihood ratio, P = .0004) was seen if abdominally obese patients were treated with prolonged cumulative PP.

Conclusion

A cautious approach to PP should be considered in abdominally obese patients.     

Plasma thrombopoietin level after liver transplantation: relationship to cold ischemia time and coagulation parameters

Objective: To determine the relation between thrombopoietin (Tpo) levels following orthotopic liver transplantation (OLT), cold ischemia time and postoperative peripheral blood platelet count and prothrombin activity.¶Design: Prospective clinical study.¶Setting: Intensive care unit.¶Patients: Fourteen patients with uncomplicated postoperative course after OLT.¶Measurements and results: Plasma Tpo, as quantified by enzyme immunoassay, rose significantly from 194.9 ± 45.7 pg/ml on day 1 after OLT to a peak value of 500.7 ± 94.1 pg/ml on day 5 while platelet count was below normal values. Then the platelet count increased and reached normal values while Tpo decreased to normal. The rise of Tpo levels was associated with normalization of prothrombin time but peak Tpo concentrations were in inverse correlation with cold ischemia times.¶Conclusion: The extent of production of Tpo in the liver graft following OLT is affected by cold ischemia time. This observation may be applicable in the prevention of bleeding complications associated with postoperative thrombocytopenia.     

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2±1.5 pg/ml) was significantly higher (P<0.05) than in pretransplantation samples (3.2±0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8±5.9 mg/dl, which was significantly higher than before transplantation (6.4±2.2 mg/dl). There was a positive correlation between the serum BUn and ET-1 (r=0.62,P<0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9±32.4%) than with those obtained before transplantation (18.3±9.2%) when compared to a standard contractility rate of 100% with 40 mM KCl. Moreover, these contractility response rates were significantly reduced (32.8±21.0%) with the addition of the ET-1 receptor antagonist FR139 317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.     

Experiences with severe P. falciparum malaria in the intensive care unit

Objective: To review the clinical profiles and therapies instituted for patients with severe malaria admitted to an ICU.¶Design: Retrospective study.¶Setting: Internal ICU of a tertiary care centre.¶Patients and participants: Between January, 1992, and February, 1999, 104 patients with malaria were admitted to the General Hospital of Vienna. Sixty-nine patients suffered from Plasmodium falciparum malaria (66 %), seven of these were admitted to the ICU.¶Measurement and results: Seven patients were admitted to the ICU, of whom three died (4 % in hospital case-fatality rate). Four patients required mechanical ventilation because of respiratory insufficiency and adult respiratory distress syndrome (ARDS), of whom three died. Three patients were treated with inhaled nitric oxide (NO) and kinetic therapy; one patient required extracorporeal veno-venous oxygenation. All patients who died required haemofiltration because of acute renal failure.¶Conclusion: As P. falciparum is a potentially life-threatening disease, reliable criteria for ICU admission should be defined and risk factors identified. Early ICU monitoring should be attempted, especially under the following conditions: (1) lack of clinical response to anti-malarial treatment within 48 h and/or (2) any signs of neurological disturbance (hypoglycaemia excluded). Prospective multicentre trials and guidelines for supportive intensive care are urgently needed.     

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure

Objective: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH).¶Design: Prospective, cohort study.¶Setting: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany.¶Subject and methods: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2)while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily.¶Main results: The mean CVVH duration was 9.8 ± 8.1 days, mortality was 65 %. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 ± 3.8 mmol/l (p < 0.001) in group 1, 20.6 ± 3.1 mmol/l in group 2 and 23.3 ± 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution.¶Conclusions: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.     

Circulating endothelin-1 and tumor necrosis factor-α: early predictors of mortality in patients with septic shock

Objectives: To determine the predictive value of early determination of tumor necrosis factor (TNF)-α, TNF-α 1 and 2 soluble receptors (sTNFR1 and sTNFR2) and endothelin-1 (ET-1) for mortality in patients with septic shock.¶Design: Prospective study.¶Setting: Intensive care unit of a university hospital.¶Patients: Twenty-one patients with septic shock.¶Interventions: None.¶Measurements and Results: Patients with septic shock had a pulmonary artery catheter inserted and blood samples drawn at time zero, 6, 12 and 24 h, simultaneously with hemodynamic assessments. Plasma levels of all markers were measured by ELISA. All patients were followed up to hospital discharge or death. Age and APACHE II scores were significantly higher in nonsurvivors (n = 11) than in survivors (n = 10). Hemodynamic assessments did not aid in the discrimination between the two groups of patients (P > 0.05). Levels of TNF-α were higher in nonsurvivors than in survivors at all time-points. sTNFR1 and sTNFR2 were also significantly elevated in nonsurvivors, but not in all measurements. Endothelin-1, however, was significantly higher in nonsurvivors than in survivors only at 6 h (P = 0.02). When both TNF-α and ET-1 were increased at early time-points, the best predictive values for mortality were obtained [positive and negative predictive values of 72 and 100 % at 6 h, odds ratio 3.0, 95 % CI (1.2–7.6)].¶Conclusions: Increased levels of TNF-α were consistently higher at all time-points in nonsurvivors with septic shock. ET-1 levels, however, appeared also to be an early and sensitive predictor of mortality. Very early determination of TNF-α and ET-1 in septic shock may help to identify patients at higher risk for adverse outcome.     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO₂/FIO₂ was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO₂/FIO₂ of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙_S/Q˙_T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved. Received: 9 April 1997 Accepted: 13 May 1997     

Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome

Objective: To determine if the plasma levels of three endothelial-specific proteins, von Willebrand factor (vWF), tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) may be useful in predicting the development of acute respiratory distress syndrome (ARDS).¶Design: Blood samples were obtained from normal healthy volunteers and on the first day from patients at risk for ARDS and those with ARDS. Daily sequential measurements of vWF and TFPI were performed in two patients.¶Setting: Normal subjects were employees at Saint Louis University Hospital, St. Louis, Missouri. Patients at risk and those with ARDS were patients admitted to the medical and surgical floors and the intensive care units at St. Louis University Hospital.¶Patients and participants: Plasma levels of vWF, TFPI and TM were measured in 27 normals, and on day 1 in 15 patients at risk for ARDS and 18 patients with ARDS from different etiologic factors.¶Measurements and results: Plasma levels of vWF were significantly elevated in the at-risk (p < 0.01) and ARDS group (p < 0.001) as compared to normals but did not differ significantly between the two groups (p > 0.05). Plasma levels of TFPI were not significantly different between the normal and the at-risk group (p > 0.05); however, they were significantly elevated in ARDS as compared with at-risk and normal groups (p < 0.001). Levels of TM were significantly increased in the at-risk group as compared to normals (p < 0.01) but were not significantly different from the ARDS group (p > 0.05). Eight patients at risk progressed to develop ARDS. A vWF level of > 300 % in patients at risk was 62 % sensitive and 71 % specific for predicting the development of ARDS with a positive predictive value of only 34 %. TFPI levels were normal in 7 of the 8 patients who developed ARDS. A TM level of > 100 ng/ml in patients at risk was 50 % sensitive and 57 % specific with a positive predictive value of merely 8 % for development of ARDS. There was no significant difference in the mean plasma levels of the three proteins on day 1 in patients at risk who developed ARDS as compared with those who did not develop ARDS. There was also no difference in mean plasma levels of the three proteins in patients with ARDS from sepsis as compared with ARDS from other etiologies. Plasma levels of vWF and TFPI correlated significantly.¶Conclusion: Plasma levels of vWF, TFPI and TM did not appear to serve as useful markers for predicting ARDS in patients at risk.     

Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro

Objective: To examine the kinetics of successful nitric oxide (NO) withdrawal in vivo and in vitro.¶Design and setting: Prospective study in a university pediatric intensive care ward and research laboratory.¶Patients and materials: Nineteen patients with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn (PPHN). Primary porcine pulmonary artery cells in vitro.¶Interventions: NO inhalation and withdrawal in patients; exposure to NO donor sodium nitroprusside (SNP) and gaseous NO in vitro.¶Measurements and results: In patients: a slight, but significant, increase of oxygenation index (OI) from 4.57 ± 0.24 cmH₂O/torr (mean ± SEM) to 4.90 ± 0.26 cmH₂O/torr after withdrawal of NO (p < 0.001). Recovery of OI (4.43 ± 0.23 cmH₂O/torr) 30 min after weaning, a significant drop after 4 h (3.72 ± 0.17 cmH₂O/torr; p < 0.001), values restored after 12 h.¶In vitro: NO synthase (NOS) activity was significantly lower in SNP-incubated cells (20.0 ± 4.0 μm/min) than in control cells (37.6 ± 7.0 μm/min; p < 0.05). Thirty minutes after SNP withdrawal there was NOS activity of 35.8 ± 10.0 μm/min with a significant increase by 4 h (p < 0.05). No alteration of endothelial NOS (ENOS) mRNA expression by NO (Northern Blot).¶Conclusion: In patients there is a slight, but significant, reversible increase of OI after successful weaning from NO. In vitro, NO leads to a reversible decrease of ENOS activity on a post mRNA level, resembling clinical observations.     

The impact of patient positioning on pressure ulcers in patients with severe ARDS: results from a multicentre randomised controlled trial on prone positioning

Purpose

Placing patients with severe acute respiratory distress syndrome (ARDS) in the prone position has been shown to improve survival as compared to the supine position. However, a higher frequency of pressure ulcers has been reported in patients in the prone position. The objective of this study was to verify the impact of prone positioning on pressure ulcers in patients with severe ARDS.

Methods

This was an ancillary study of a prospective multicentre randomised controlled trial in patients with severe ARDS in which the early application of long prone-positioning sessions was compared to supine positioning in terms of mortality. Pressure ulcers were assessed at the time of randomisation, 7 days later and on discharge from the intensive care unit (ICU), using the four-stage Pressure Ulcers Advisory Panel system. The primary end-point was the incidence (with reference to 1,000 days of invasive mechanical ventilation or 1,000 days of ICU stay) of new patients with pressure ulcers at stage 2 or higher from randomisation to ICU discharge.

Results

At randomisation, of the 229 patients allocated to the supine position and the 237 patients allocated to the prone position, the number of patients with pressure ulcers was not significantly different between groups. The incidence of new patients with pressure ulcers from randomisation to ICU discharge was 20.80 and 14.26/1,000 days of invasive mechanical ventilation (P = 0.061) and 13.92 and 7.72/1,000 of ICU days (P = 0.002) in the prone and supine groups, respectively. Position group [odds ratio (OR) 1.5408, P = 0.0653], age >60 years (OR 1.5340, P = 0.0019), female gender (OR 0.5075, P = 0.019), body mass index of >28.4 kg/m² (OR 1.9804, P = 0.0037), and a Simplified Acute Physiology Score II at inclusion of >46 (OR 1.2765, P = 0.3158) were the covariates independently associated to the acquisition of pressure ulcers.

Conclusion

In patients with severe ARDS, prone positioning was associated with a higher frequency of pressure ulcers than the supine position. Prone positioning improves survival in patients with severe ARDS and, therefore, survivors who received this intervention had a greater likelihood of having pressure ulcers documented as part of their follow-up. There are risk groups for the development of pressure ulcers in severe ARDS, and these patients need surveillance and active prevention.     

The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats

Objective: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats.¶Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure–intracranial pressure) with norepinephrine (0.08 μg · kg^?1· min^?1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ET_A/B receptor antagonist, bosentan, i. v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique.¶Results: During the control test, norepinephrine infusion increased CPP by 21 ± 2 (23 ± 2 %) mmHg (mean ± SEM; p < 0.001) and CBF by 3.6 ± 3.1 (6 ± 8 %) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 ± 1 (20 ± 2 %) mmHg (p < 0.001) and CBF by 15.8 ± 4.1 (46 ± 13 %) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaC0₂ levels were stable during the tests (40.2 ± 1.4 mmHg).¶Conclusions: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.     

Improvement in oxygenation by prone position and nitric oxide in patients with acute respiratory distress syndrome

Objective: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. Design: Prospective clinical study. Setting: General intensive care service in a community teaching hospital. Patients: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23 ± 0.27). Measurements and results: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a ≥ 20 % increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO₂/FIO₂). In the prone position PaO₂/FIO₂ increased significantly (from 110 ± 55 to 161 ± 89 mmHg, p < 0.01) and venous admixture decreased (from 38 ± 12 to 30 ± 7 %, p < 0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO₂/FIO₂ to 134 ± 64 mmHg (p < 0.01) and decreasing venous admixture to 35 ± 12 %, (p < 0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO₂/FIO₂ (197 ± 92 mmHg) and decreasing venous admixture (27 ± 8 %) (p < 0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO₂/FIO₂ were correlated to changes in pulmonary vascular resistance only in the prone position. Conclusions: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation. Received: 15 June 1998 Final revision received: 13 October 1998 Accepted: 30 October 1998     

Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver

Abstract. The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P<0.01) higher than in controls both before (ET-1, 19.6 ± 1.3pgmL^-1 vs. 11.8 ± 0.4pgmL^-1; ET-3, 18.5±1.4pgmL^-1 vs. 9.5 ± 0.5 pgmL^-1) and after water immersion (ET-1, 18.6± 1.2 pgmL^-1 vs. 12.4±0.3 pgmL^-1; ET-3,18.7 ± 1.7pgmL^-1 vs. 10.0±0.5pg mL^-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r= 0.79, P<0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r= 0.65, P<0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r= -0.55, P<0.01 and r= -0.50, P<0.05, respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 ± 1.0 pgmL^-1 vs. 15.5±0.4pg mL^-1, P< 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.     

Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management

Objective: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI).¶Design: Prospective, interventional study.¶Setting: Intensive care unit in a university hospital.¶Patients: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3–8).¶Interventions: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if %CPP/%CVR ≤ 2.¶Results: Cerebral blood flow (CBF: Xe¹³³ inhalation technique), jugular bulb oxygen saturation (SjO₂) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % ( ± 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 ± 3 to 28 ± 3 ml/100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO₂ did not change significantly from baseline. TCD remained within the normal range.¶Conclusions: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.     

Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome

Objective: We performed a follow-up cohort analysis in order to delineate the correlation between pulmonary function (PF) and health-related quality of life (HRQL) in patients after ARDS.¶Design: Follow-up cohort study.¶Setting: A 20-bed ICU of a university teaching hospital.¶Patients: A cohort of 50 long-term survivors of ARDS.¶Measurements and results: Measurements of PF (FVC, FEV₁, TLC, D_LCO) and HRQL (SF-36 Health Status Questionnaire) were made 5.5 years (median value) after discharge from the ICU. Impairments in PF (defined as PF results below 80 % of the predicted value) were frequent but generally mild. Twenty patients had a single PF impairment (with limitations in FEV1/FVC ratio in 12 patients being the most common), four patients had two (with D_LCO and FEV1/FVC ratio impairment the most common) and three patients had pathologic results in three PF tests (FEV₁/FVC ratio, TLC and capillary pO₂ during exercise in one case, FVC, TLC and capillary pO₂ during exercise in the second patient and FVC, TLC and D_LCO in the third). Compared to normal controls, survivors of ARDS showed impairments in all SF-36 health dimensions (p < 0.001). Patients with multiple (> 1) PF impairments described the lowest HRQL with major limitations in all SF-36 categories (p < 0.037) including physical and mental summary scores (36.5 vs 46.9, p = 0.037 and 31.3 vs 51.4, p = 0.003) when compared to patients with no or only one PF impairment.¶Conclusions: Long-term survivors of ARDS have a significant reduction in HRQL and the presence of multiple PF impairments is associated with maximal decrements in HRQL.