Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease

Objective: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). Design: Prospective clinical study. Setting: General intensive care unit in Sabadell, Spain. Patients: Nine mechanically ventilated COPD patients (mean age 72±2 years; forced expiratory volume in 1 s 0.91±0.11 l) and nine ARDS patients (mean age 57±6 years; mean lung injury score 2.8±0.1) Measurements and results: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO₂). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO₂/FIO₂ (fractional inspired oxygen) 190±18 mmHg) than in the ARDS group (PaO₂/FIO₂ 98±12 mmHg), (p<0.01). After NO-10, PaO₂/FIO₂ increased (to 141±17 mmHg, p<0.01) and Qva/Qt decreased (39±3 to 34±3%, p<0.01) in the ARDS group. There were no changes in PaO₂/FIO₂ and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO₂/FIO₂ was not correlated with basal PaO₂/FIO₂. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p=0.05). Conclusions: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease. Received: 19 December 1995 Accepted: 28 September 1996     

Acute effects of continuous rotational therapy on ventilation-perfusion inequality in lung injury

Objective: To investigate ventilation-perfusion (V_A/Q) relationships, during continuous axial rotation and in the supine position, in patients with acute lung injury (ALI) using the multiple inert gas elimination technique. Design: Prospective investigation. Setting: Eighteen-bed intensive care unit in a university hospital. Patients and interventions: Ten patients with ALI (PaO₂/FIO₂ ratio < 300 mm Hg) were mechanically ventilated in a pressure controlled mode and placed on a kinetic treatment table. Measurements and results: Distributions of V_A/Q were determined 1) during rotation (after a period of 20 min) and 2) after a resting period of 20 min in the supine position. During axial rotation, intrapulmonary shunt (19.1 ± 15 % of cardiac output) was significantly reduced in comparison with when in the supine position (23 ± 14 %, p < 0.05), areas with “low” V_A/Q were not affected by the positioning maneuver. General V_A/Q mismatch (logarithmic distribution of pulmonary blood flow) was decreased during rotation (0.87 ± 0.37) in comparison with when the patient was in the supine position (0.93 ± 0.37, p < 0.05). Arterial oxygenation was significantly improved during continuous rotation (PaO₂/FIO₂ = 217 ± 137 mm Hg) as compared with in the supine position (PaO₂/FIO₂ = 174 ± 82 mm Hg, p < 0.05). The positive response of the continuous rotation on arterial oxygenation was only demonstrated in patients with a Murray Score of 2.5 or less, indicating a “mild to moderate” lung injury, while in patients presenting with progressive ARDS (Murray Score > 2.5), the acute positive response was limited. Conclusions: Continuous axial rotation might be a method for an acute reduction of V_A/Q mismatch in patients with mild to moderate ALI, but this technique is not effective in late or progressive ARDS. Further studies including a large data collection are needed. Received: 19 June 1997 Accepted: 6 November 1997     

Long chain versus medium chain lipids in patients with ARDS: effects on pulmonary haemodynamics and gas exchange

Objective: To compare pulmonary haemodynamic and gas exchange alterations in septic patients with ARDS receiving long-chain triglycerides (LCT) versus medium-chain triglycerides (MCT). Design: Prospective, randomised, clinical study. Setting: Surgical ICU patients in a University Hospital. Patients: Twenty-one septic patients with ARDS were randomly assigned to receive 50 % of their non-protein caloric requirements as either 20 % LCT (group 1, n = 10) or 20 % 1 : 1 mixture of LCT/MCT (group 2, n = 11). Intervention: Intravenous infusion of LCT and LCT/MCT combinations at a rate of 12 g · h^{− 1}. Measurements and results: The LCT infusion was associated with an increase of pulmonary venous admixture (Qva/Qt) from 24 % ± 5 % to 37 % ± 6 %, an increase of mean pulmonary artery pressure (MPAP) from 25 ± 5 to 33 ± 4 mmHg and decrease of PaO₂/FIO₂ from 240 ± 30 to 180 ± 35. LCT/MCT administration was only associated with an elevation of oxygen consumption (VO₂) from 329 ± 14 to 396 ± 12 ml/min. During lipid infusion group 1 patients presented higher Qva/Qt (37 % ± 6 % vs 25 % ± 4 %), MPAP (33 ± 4 vs 27 ± 3 mmHg) and VO₂ (359 ± 11 vs 396 ± 12 ml/min) and lower PaO₂/FIO₂ (180 ± 35 vs 235 ± 30) values compared to group 2. Conclusion: In conclusion, we have shown that, in septic patients with respiratory failure, LCT administration was associated with more significant changes of Qva/Qt, MPAP and PaO₂/FIO₂ compared to infusion of an LCT/MCT 1 : 1 emulsion. Clinically, these transient alterations might cause serious problems in patients with marginal arterial oxygenation and cardio-respiratory impairment. Received: 23 July 1997 Accepted: 15 May 1998     

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. Received: 18 April 1999 Final revision received: 30 June 1999 Accepted: 9 July 1999     

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     

Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange

Objective To evaluate the effect of extracorporeal gas exchange (ECMO) on mortality of patients referred with severe acute respiratory distress syndrome (ARDS).Design and setting Prospective observational study in a university hospital ICU.Patients 150 patients with severe ARDS.Interventions Multimodal treatment with and without ECMO.Measurements and main results We treated 118 patients (78.7%) conservatively and 32 patients with ECMO. Patients in the ECMO group presented with significantly more severe disease (lung injury score 3.8 ± 0.3 vs. 3.3 ± 0.4; SOFA score 52 ± 14 vs. 43 ± 12; and SAPS score 14 ± 3.3 vs. 10 ± 3.5). Mortality in ECMO-treated patients tended to be higher than that with conservative treatment (46.9% vs. 28.8%, p = 0.059). Multivariate logistic regression analyses with backward selection excluded ECMO as predictor of mortality (p = 0.79). Independent predictors of mortality were age (odds ratio 1.044, 95% confidence interval 1.014–1.075, p = 0.004), mean pulmonary artery pressure (1.082, 1.026–1.141, p = 0.036), sequential organ failure assessment score (1.148, 1.018–1.294, p = 0.024), and days of mechanical ventilation prior to referral (1.064, 1.008–1.123, p = 0.025).Conclusion ECMO treatment does not predict mortality in patients with most severe ARDS.     

Hemodynamic profile in severe ARDS: results of the European Collaborative ARDS Study

Objective: Although the acute respiratory distress syndrome (ARDS) was identified as long as 30 years ago, potential therapeutic objectives have been defined from small series rather than large trials. Moreover, relationships between ARDS and hemodynamics are unclear. The European Collaborative ARDS Study was designed to identify factors influencing the pathogenesis, severity, and prognosis of ARDS. Analysis of the hemodynamic profiles collected during this study and of their contribution to the above-mentioned facets of ARDS is the focus of the present report. Design: Prospective clinical study. Setting: 38 European intensive care units (ICUs). Patients and methods: We collected 2758 sets of data from 586 patients, including baseline data, data on proven or suspected causes of ARDS differentiating direct and nondirect lung injury, and data on baseline status including multiple organ dysfunction (MOD) with differentiation of primary ARDS from ARDS secondary to severe systemic disorders. Events during follow-up were also recorded, including whether the acute respiratory failure did or did not improve after 24 h (groups A and B, respectively). When available, hemodynamic data were recorded at enrollment (day 0), on days 1–3, 7, 14, and 21, and at discharge or at the time of death in the ICU. Results: Although the rate of preexisting disease and the nature and rate of complications varied widely among etiologic categories, differences in the hemodynamic profile occurred only between primary and secondary ARDS. Both at inclusion and during the course of the illness, variables that were used to investigate Va/Q mismatch [arterial oxygen tension (PaO₂, arterial oxygen saturation, right-to-left shunt, and the PaO₂/fractional inspired oxygen (FIO₂) ratio] predicted survival. High pulmonary artery pressure (PAP) and low systemic artery pressure (SAP) were also related to the prognosis. In the logistic regression model including hemodynamic and oxygen-related variables, however, the only independent predictors of survival were the ratio of right over left ventricular stroke work (RVSW/LVSW) and the PaO₂/FIO₂ ratio at admission. On day 2, the best prognostic model included: age [odds ratio (OR) = 1.04, p = 0.0004], opportunistic pneumonia as the cause of ARDS (OR = 3.2, p = 0.03), existence of MOD (OR = 1.9, p = 0.03), PaO₂/FIO₂ (OR = 0.96, p = 0.005), and RVSW/LVSW (OR = 25, p = 0.02). A high RVSW/LVSW ratio, high systolic PAP, low diastolic SAP, and low PaO₂/FIO₂, and increased right atrial pressure were negative prognostic indicators during follow-up. Conclusion: In addition to the cause of ARDS and the early time-course of lung function, a high systolic PAP and a low diastolic SAP were strong independent indicators of survival. Received: 6 November 1997 Accepted: 8 July 1998     

Noninvasive ventilation for the treatment of acute respiratory failure in patients with hematologic malignancies: a pilot study

Objective: To evaluate treatment with noninvasive ventilation (NIV) by nasal mask as an alternative to endotracheal intubation and conventional mechanical ventilation in patients with hematologic malignancies complicated by acute respiratory failure to decrease the risk of hemorrhagic complications and increase clinical tolerance. Design: Prospective clinical study. Setting: Hematologic and general intensive care unit (ICU), University of Rome “La Sapienza”. Patients: 16 consecutive patients with acute respiratory failure complicating hematologic malignancies. Interventions: NIV was delivered via nasal mask by means of a BiPAP ventilator (Respironics, USA); we evaluated the effects on blood gases, respiratory rate, and hemodynamics along with tolerance, complications, and outcome. Measurements and results: 15 of the 16 patients showed a significant improvement in blood gases and respiratory rate within the first 24 h of treatment. Arterial oxygen tension (PaO₂), PaO₂/FIO₂ (fractional inspired oxygen) ratio, and arterial oxygen saturation significantly improved after 1 h of treatment (43 ± 10 vs 88 ± 37 mmHg; 87 ± 22 vs 175 ± 64; 81 ± 9 vs 95 ± 4 %, respectively) and continued to improve in the following 24 h (p < 0.01). Five patients died in the ICU following complications independent of the respiratory failure, while 11 were discharged from the ICU in stable condition after a mean stay of 4.3 ± 2.4 days and were discharged in good condition from the hospital. Conclusions: NIV by nasal mask proved to be feasible and appropriate for the treatment of respiratory failure in hematologic patients who were at high risk of intubation – related complications. Received: 21 April 1998 Accepted: 18 September 1998     

Impact of positive end-expiratory pressure on the definition of acute respiratory distress syndrome

Objective We examined whether PEEP during the first hours of ARDS can induce such a change in oxygenation that could mask fulfillment of the AECC criteria of a PaO₂/FIO₂ 200 essential for ARDS diagnosis.Design and setting Observational, prospective cohort in two medical-surgical ICU in teaching hospitals.Patients 48 consecutive patients who met AECC criteria of ARDS on 0 PEEP (ZEEP) at the moment of diagnosis.Measurements and results PaO₂/FIO₂ and lung mechanics were recorded on admission (0 h) to the ICU on ZEEP, and after 6, 12, and 24 h on PEEP levels selected by attending physicians. Lung Injury Score (LIS) was calculated at 0 and 24 h. PaO₂/FIO₂ rose significantly from 121±45 on ZEEP at 0 h, to 234±85 on PEEP of 12.8±3.7 cmH₂O after 24 h. LIS did not change significantly (2.34±0.53 vs. 2.42±0.62). These variables behaved similarly in pulmonary and extrapulmonary ARDS, and in survivors and nonsurvivors. After 24 h only 18 patients (38%) still had a PaO₂/FIO₂ of 200 or lower. Their mortality was similar to that in the remaining patients (61% vs. 53%).Conclusions The use of PEEP improved oxygenation such that one-half of patients after 6 h, and most after 24 h did not fulfill AECC hypoxemia criteria of ARDS. However, LIS remained stable in the overall series. These results suggest that PEEP level should be taken into consideration for ARDS diagnosis.     

Transcutaneous Pco2 and Po2: A multicenter study of accuracy

A multicentcr study used 756 samples from 251 patients in 12 institutions to compare arterial (PaO₂, PaCO₂) with transcutaneous (PsO₂, PsCO₂) oxygen and carbon dioxide tensions, measured usually at 44°C. Of these samples, 336 were obtained from 116 neonates, 27 from 25 children with cystic fibrosis, and 140 from 40 patients under general anesthesia. Ninety-one patients were between 4 weeks and 18 years of age, 32 were between 18 and 60 years, and 12 were over 60. The ratio of transcutaneous to arterial P(s/a)CO₂ was 1.01 ±0.11 with PaCO₂ less than 30 mm Hg, increasing to 1.04 ±0.08 at PaCO₂ greater than 40 mm Hg. Mean bias and its standard deviation (PsCO₂ — PaCO₂) were + 1.3 ± 3.9 mm Hg in the entire group, + 1.8 ± 4.2 mm Hg in neonates (NS). Bias was +0.2 ± 2.7 mm Hg when PaCO₂ was less than 30 mm Hg (N = 175, NS), 1.0 ± 3.4 with 30 < PaCO₂ < 40 (n = 329,p < 0.001), and +2.04 ± 4.00 mm Hg with 40 < PaCO₂ < 70 (n = 229,p < 0.001). These data suggest that, using transcutaneous PCO₂ monitors with inbuilt temperature correction of 4.5%/‡C, the skin metabolic offset should be set to 6 mm Hg. The linear regression was PsCO₂ =1.052(PaCO₂)-0.56, Sy·x = 3.92, R = 0.929 (n = 756); and PsCO₂ = 1.09(PaCO₂)-1.57, Sy·x = 4.17, R = 0.928 in neonates (n = 336). The use of vasopressors and vasodilators had no significant effect on bias or its standard deviation or on regression slope and intercept (n = 78). In cystic fibrosis patients, bias and standard deviation were 0.0 ± 1.7 mm Hg (n = 27). Under anesthesia, PsCO₂ = 1.07PaCO₂-1.58, with bias and standard deviation = 0.6 ± 3.5 (n = 140). For oxygen, at PaO₂ ≤ 80 the ratio P(s/a)O₂ = 1.05 ± 0.16 in nconates and 0.93 ± 0.21 in older patients, but when PaO₂ > 80, P(s/a)O₂ fell to 0.88 ± 0.18 in neonates and 0.74 ± 0.21 in older patients. The errors were significantly greater (p < 0.001) in older patients than in neonates above but not below 80 mm Hg, and within both groups errors were significantly greater above than below 80 mm Hg.     

Reduction of ventilator settings allowed by intravenous oxygenator (IVOX) in ARDS patients

Objective To evaluate the possibility of reducing ventilator settings to “safe” levels by extrapulmonary gas exchange with IVOX in ARDS patients. Design Uncontrolled open clinical study. Setting Medical Intensive Care Unit of a University Hospital. Patients 6 patients with ARDS who entered into IVOX phase II clinical trials. Interventions The end-point of this study was to reduce ventilator settings from the initial values, recorded on the day of inclusion, to the following: peak inspiratory pressure <40 cmH₂O, mean airway pressure <25 cmH₂O and tidal volume <10 ml/kg. Trials to achieve this goal were made on volume-controlled ventilation within the 24h before and after IVOX insertion. Comparison of the results achieved during these trials used wilcoxon test. Results Before IVOX implantation reduction of ventilator settings was not possible in the 6 patients, despite a non-significant increase in PaO₂/FIO₂ was achieved. IVOX permitted significant decrease in PaCO₂ (from 60.5±15 to 52±11 mmHg;p=0.02) before any modification of the ventilatory mode. After IVOX insertion, a significant decrease of the ventilator settings was performed: peak and mean airway pressures dropped from 44±10 to 36.8±6.7;p=0.02 and from 26.3±5.6 to 22.5±3.9 cmH₂O;p=0.02, respectively. Concommitantly, PaCO₂ remained unchanged and PaO₂/FIO₂ increased significantly from 93±28 to 117±52;p=0.04. The interruption of oxygen flow on IVOX was associated with a slight decrease of the oxygen variables. Tolerance of IVOX was satisfactory. However, a significant decrease both in cardiac index and in pulmonary wedge pressures (from 4.5±1.2 to 3.4±9;p=0.03 and from 16±5 to 11±2;p=0.04, respectively) was observed. Conclusion Gas exchange achieved by IVOX allowed reduction of ventilator settings in 6 ARDS patients in whom previous attempts have failed. CO₂ removal by the device, may explain these results. Efficacy of IVOX on arterial oxygenation was uncertain.     

The impact of respiratory variables on mortality in non-ARDS and ARDS patients requiring mechanical ventilation

Objectives: Primarily, to determine if respiratory variables, assessed on a daily basis on days 1–6 after ICU admission, were associated with mortality in non-ARDS and ARDS patients with respiratory failure requiring mechanical ventilation. Secondarily, to determine non-respiratory factors associated with mortality in ARDS and non-ARDS patients. Design: Prospective multicentre clinical study. Setting: Seventy-eight intensive care units in Sweden and Iceland. Patients: Five hundred twenty non-ARDS and 95 ARDS patients. Measurements and results: Potentially prognostic factors present at inclusion were tested against 90-day mortality using a Cox regression model. Respiratory variables (PaO₂/FIO₂, PEEP, mean airway pressure (MAP) and base excess (BE)) were tested against mortality using the model. Primary aim: in non-ARDS a low PaO₂/FIO₂ on day 1, RR (risk ratio) = 1.17, CI (95 % confidence interval) (1.00; 1.36), day 4, 1.24 (1.02; 1.50), day 5, 1.25 (1.02; 1.53) and a low MAP at baseline, 1.18 (1.00; 1.39), day 2, 1.24 (1.02; 1.52), day 3, 1.33 (1.06; 1.67), day 6, 2.38 (1.11; 5.73) were significantly associated with 90-day death. Secondary aim: in non-ARDS a low age, RR = 0.77 (0.67; 0.89), female gender, 0.85 (0.74; 0.98), and low APS (acute physiologic score), 0.85 (0.73; 0.99), were associated with survival; chronic disease, 1.31 (1.12; 1.52), and non-pulmonary origin to the respiratory failure, 1.27 (1.10; 1.47), with death. In ARDS low age, RR = 0.65 CI (0.46; 0.91), and low APS, 0.65 (0.46; 0.90), were associated with survival. Conclusions: No independent significant association was seen between 90-day mortality and degree of hypoxaemia, PEEP, MAP or BE for the first full week of ICU care in either ARDS or non-ARDS. In a sub-group of non-ARDS a lower PaO₂/FIO₂ and MAP tended to influence mortality where a significant association was seen for 3 of 7 study days. Age, gender, APS, presence of a chronic disease and a pulmonary/non-pulmonary reason for the respiratory failure were associated with mortality in non-ARDS, while only age and APS showed a similar association in ARDS. Received: 16 February 1999 Final revision received: 4 October 1999 Accepted: 24 February 2000     

Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children

Objective To evaluate the effect of terlipressin on oxygenation, PaO₂/FIO₂, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline. Design and setting A randomized, nonblind study in the pediatric intensive care unit of a university hospital. Patients and measurements We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n = 30) or control (n = 28). TP was administered as intravenous bolus doses of 20 μg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO₂/FIO₂ rates, length of stay, and mortality rate in PICU were recorded prospectively. Results Mean arterial pressure and PaO₂/FIO₂ significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4 ± 7.9 vs. 20.2 ± 9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4 ± 6.9 vs. 6.2 ± 3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin. Conclusions Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO₂/FIO₂, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock.     

Prognosis value of partial arterial oxygen pressure in patients with septic shock subjected to pre-hospital invasive ventilation

Objective

Mechanical ventilation can help improve the prognosis of septic shock. While adequate delivery of oxygen to the tissue is crucial, hyperoxemia may be deleterious. Invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. We propose to determine whether the arterial oxygen pressure (PaO₂) at the intensive care unit (ICU) admission is associated with mortality in patients with septic shock subjected to pre-hospital mechanical ventilation.

The open lung concept: pressure controlled ventilation is as effective as high frequency oscillatory ventilation in improving gas exchange and lung mechanics in surfactant-deficient animals

Objective: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. Design: Prospective, randomized, animal study. Setting: Experimental laboratory of a university. Subjects: 18 adult male Sprague-Dawley rats. Interventions: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFO_OLC). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO₂/FIO₂) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO₂/FIO₂ L 500 mm Hg. Pressure amplitude was adjusted to keep CO₂ as close as possible in the normal range. Measurements and results: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO₂/FIO₂ L 500 mm Hg was 25 ± 1.3 cm H₂O during PCV_OLC and 25 ± 0.5 cm H₂O during HFOV_OLC. Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. Conclusions: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV. Received: 14 October 1998 Final revision received: 11 April 1999 Accepted: 25 June 1999     

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.     

Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients

Objective: To evaluate the prevalence and outcome of the acute respiratory distress syndrome (ARDS) among patients requiring mechanical ventilation. Design: A prospective, multi-institutional, initial cohort study including 28-day follow-up. Settings: Thirty-six French intensive care units (ICUs) from a working group of the French Intensive Care Society (SRLF). Patients: All the patients entering the ICUs during a 14-day period were screened prospectively. Hypoxemic patients, defined as having a PaO₂/FIO₂ ratio (P/F) of 300 mmHg or less and receiving mechanical ventilation, were classified into three groups, according to the Consensus Conference on ARDS: group 1 refers to ARDS (P/F: 200 mmHg or less and bilateral infiltrates on the chest X-ray); group 2 to acute lung injury (ALI) without having criteria for ARDS (200 < P/F ≤ 300 mmHg and bilateral infiltrates) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups. Results: Nine hundred seventy-six patients entered the ICUs during the study period, 43 % of them being mechanically ventilated and 213 (22 %) meeting the criteria for one of the three groups. Among all the ICU admissions, ARDS, ALI and group 3 patients amounted, respectively, to 6.9 % (67), 1.8 % (17) and 13.3 % (129) of the patients, and represented 31.5 %, 8.1 % and 60.2 % of the hypoxemic, ventilated patients. The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others (60 % vs 31 % p < 0.01). In group 3, 42 patients had P/F less than 200 mmHg associated with unilateral lung injury; mortality was significantly lower (40.5 %) than in the ARDS group. In the whole group of hypoxemic, ventilated patients, septic shock and severity indices but not oxygenation indices were significantly associated with mortality, while the association with immunosuppression revealed only a trend (p = 0.06). Conclusions: In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high. Received: 21 September 1998 Final revision received: 3 February 1999 Accepted: 3 May 1999     

Regional distribution of gas and tissue in acute respiratory distress syndrome. II. Physiological correlations and definition of an ARDS Severity Score

Objectives: (a) To assess whether differences in lung morphology observed in patients with adult respiratory distress syndrome (ARDS) are associated with differences in cardiorespiratory parameters, lung mechanics, and outcome. (b) To propose a new ARDS Severity Score to identify patients with a high mortality risk. Design: Prospective study over a 53-month period. Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS. Measurements and results: Cardiorespiratory parameters were measured using a Swan-Ganz catheter, the pressure-volume (PV) curve was measured using the gross syringe method, and fast spiral computed tomography (CT) was performed. Patients with diffuse attenuations (n = 16) differed from patients with lobar attenuations (n = 26) regarding: (a) mortality rate (75 % vs. 42 %, p = 0.05), (b) incidence of primary ARDS (82 % vs. 50 %, p = 0.03), (c) respiratory compliance (47 ± 12 vs. 64 ± 16 ml per cmH₂O^–1 p = 0.04), and (d) lower inflexion point (8.4 ± 2.0 vs. 4.6 ± 2.0 cmH₂O, p = 0.001). A third group of patients with patchy attenuations (n = 29) had a mortality rate of 41 %, a respiratory compliance of 56 ± 18 ml per cmH₂O^–1 and a lower inflexion point of 6.3 ± 2.7 cmH₂O. The bedside chest radiograph accurately assessed lung morphology in only 42 % of the patients. In contrast to the scores based on the bedside chest radiograph, a new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters identified a subgroup of patients with a high mortality rate (≥ 60 %). Conclusions: In patients with ARDS, differences in lung morphology are associated with differences in outcome and lung mechanics. A new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters accurately identified patients with the most severe forms of ARDS and a mortality rate above 60 %. Received: 12 May 1999 Final revision received: 9 February 2000 Accepted: 10 April 2000     

Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults

Purpose

This study was designed to optimize the latest generation venovenous (vv)-extracorporeal membrane oxygenation (ECMO)-circuit configuration and settings based on the evaluation of blood oxygenation and CO₂ removal determinants in patients with severe acute respiratory distress syndrome (ARDS) on ultraprotective mechanical ventilation.

Methods

Blood gases and hemodynamic parameters were evaluated after changing one of three ECMO settings, namely, circuit blood flow, FiO_2ECMO (fraction of inspired oxygen in circuit), or sweep gas flow ventilating the membrane, while leaving the other two parameters at their maximum setting.

Results

Ten mechanically ventilated ARDS patients (mean age 44 ± 16 years; 6 males; mean hemoglobin 8.0 ± 1.8 g/dL) on ECMO for a mean of 9.0 ± 3.8 days) receiving femoro–jugular vv-ECMO were evaluated. vv-ECMO blood flow and FiO_2ECMO determined arterial oxygenation. Decreasing the ECMO flow from its baseline maximum value (5.8 ± 0.8 L/min) to 40 % less (2.4 ± 0.3 L/min) significantly decreased mean PaO₂ (arterial oxygen tension; 88 ± 24 to 45 ± 9 mm Hg; p < 0.001) and SaO₂ (oxygen saturation; 97 ± 2 to 82 ± 10 %; p < 0.001). When the ECMO flow/cardiac output was >60 %, SaO₂ was always >90 %. Alternatively, the rate of sweep gas flow through the membrane lung determined blood decarboxylation, while PaCO₂ (arterial carbon dioxide tension) was unaffected when the ECMO blood flow and FiO_2ECMO were reduced to <2.5 L/min and 40 %, respectively. In three additional patients evaluated before and after red blood cell transfusion, O₂ delivery increased after transfusion, allowing lower ECMO flows to reach adequate SaO₂.

Conclusions

For severe ARDS patients receiving femoro–jugular vv-ECMO, blood flow was the main determinant of arterial oxygenation, while CO₂ elimination depended on sweep gas flow through the oxygenator. An ECMO flow/cardiac output >60 % was constantly associated with adequate blood oxygenation and oxygen transport and delivery.     

Augmentation of Pulmonary Perfusion by Conducted Effects of a Pulmonary Artery Ultrasound Catheter

Ultrasound (US) generated by catheters used clinically for US-facilitated thrombolysis can release shear-dependent vasodilators from endothelial and red blood cells. We hypothesized that catheter-based US in the pulmonary artery (PA) decreases downstream vascular resistance and increases pulmonary blood flow. In rhesus macaques, a U.S. Food and Drug Administration-approved multi-element US catheter was placed in a pulmonary artery. Comprehensive echocardiography was performed (i) at baseline, (ii) during hypoxemia (12% FIO₂) to increase pulmonary vascular resistance (PVR) and (c) 15 min after initiating US during hypoxemia. Reduced FIO₂ produced intended reductions in oxygen saturation (69 ± 3%) and PaO₂ (34 ± 5 mm Hg), yet on echocardiography, hypoxemia did not create the intended model, with only modest hypoxia-related increases in PA systolic pressure (24 ± 4 to 28 ± 4 mm Hg, p = 0.05) and no significant change in PVR or multiparametric right ventricular (RV) function. Although US did not further change total PVR, on ^99mTc-macroalbumin aggregate single-photon-emission computed tomography imaging, lung perfusion was significantly higher in the lung ipsilateral to the US catheter versus the contralateral control lung (133 ± 48 cpm vs. 103 ± 43 × 10³ cpm, p = 0.01). We conclude that PA catheter-based US increases regional lung perfusion, most likely from vasodilators that are conducted downstream.