Difference in early all-cause mortality among patients having hip arthroplasty a Swedish perioperative registry study 2013-2022.

INTRODUCTION: Hip arthroplasty is a common orthopaedic procedure worldwide. There is an ongoing debate related to the fixation and anaesthesia impact on the 30-day mortality, particularly in the aging population with higher American Society of Anaesthesiology (ASA) Physical-Status. AIM: To study the 30-day all-cause mortality in patients undergoing primary hip arthroplasty, with regards to the impact of age, ASA-class, anaesthesia techniques, indication for surgery and fixation techniques. MATERIALS AND METHODS: Perioperative data for primary hip arthroplasty procedures for osteoarthritis and hip fractures registered in the Swedish Perioperative Registry (SPOR) between 2013 and June 2022 were collected. Binary logistic regressions were performed to assess the impact of age, ASA-class, anaesthetic technique, indication for surgery and fixation on odds ratio for 30-day mortality in Sweden. RESULTS: In total, 79,114 patients, 49,565 with osteoarthritis and 29,549 with hip fractures were included in the main study cohort. Mortality was significantly higher among hip fracture patients compared with osteoarthritis, cumulative 8.2% versus 0.1% at 30-days respectively (p < 0.001). Age above 80 years (OR3.7), ASA 3-5 (OR3.3) and surgery for hip fracture (OR 21.5) were associated with significantly higher odds ratio, while hybrid fixation was associated with a significantly lower odds ratio (OR0.4) of 30-day mortality. In the same model, for the subgroups of osteoarthritis and hip fracture, only age (OR 3.7) and ASA-class (OR 3.3) had significant impact, increasing the odds ratio for 30-day mortality. Hemi arthroplasty was commonly used among the hip fracture patients 20.453 (69.2%), and associated with a significantly higher odds ratio for all-cause 30-day mortality as compared to total hip arthroplasty when adjusting for age and ASA-class and fixation 2.3 (95%CI 1.9-2.3, p < 0.001). CONCLUSIONS: All-cause 30-day mortality associated with arthroplasty differed significantly between the two cohorts, hip fracture, and osteoarthritis (8.2% and 0.1% respectively) and mortality expectedly increased with age and higher ASA-class. Anaesthetic method and cement-fixation did not impact the odds ratio for all-cause 30-day mortality after adjustment for age and ASA-class.

Effect of lipopolysaccharide administration on the number, phenotype and content of nuclear molecules in blood microparticles of normal human subjects.

Microparticles (MPs) are small membrane-bound vesicles that arise from activated and dying cells and promote inflammation and thrombosis. To characterize the in vivo release of MPs, we used flow cytometry to measure MPs in the blood of 15 healthy volunteers administered bacterial endotoxin (lipopolysaccharide or LPS) in the presence of a low dose of hydrocortisone with or without inhaled nitric oxide. MPs, defined as particles less than 1.0 µm in size, were assessed following labelling for CD42a, CD14 and CD62E or CD144 antibodies to identify MPs from platelets (PMPs), monocytes (MMPs) and endothelial cells (EMPs). In addition, PMPs and MMPs were labelled with anti-HMGB1 and stained with SYTO13 to assess nuclear acid content. Administration of LPS led to an increase in the numbers of PMPs, MMPs and EMPs as defined by CD62E, as well as the number of MMPs and PMPs staining with anti-HMGB1 and SYTO13. Inhalation of NO did not influence these findings. Together, these studies show that LPS can increase levels of blood MPs and influence phenotype, including nuclear content. As such, particles may be a source of HMGB1 and other nuclear molecules in the blood during inflammation.

Immunomodulation by a combination of nitric oxide and glucocorticoids in a human endotoxin model.

BACKGROUND: inflammatory reactions arise in reaction to a variety of pathogenic insults. The combination of inhaled nitric oxide (iNO) and glucocorticoids (GC) may attenuate endotoxin-induced inflammatory responses. It has been shown that the combination of iNO (30 p.p.m.) and steroids blunted the inflammatory response in a porcine endotoxin model, but not in humans. Therefore, we investigated whether a clinically 'maximal' dose of iNO in combination with GC could modulate the systemic inflammatory response in a human endotoxin model. METHODS: a double-blind, cross-over, placebo-controlled randomized study including 15 healthy Caucasian volunteers (five females, 10 males). Performed at the Intensive Care Unit in a university hospital. iNO 80 p.p.m. or placebo (nitrogen) was started 2h before administration of endotoxin (2 ng/kg). Thirty minutes later, GC (2mg/kg, hydrocortisone) was administered intravenously. Blood samples and clinical signs were collected before and up to 24 h after the endotoxin injection. RESULTS: body temperature and heart rate increased significantly subsequent to endotoxin challenge. The plasma levels of IFN-γ, IL-1ß, IL-2, 4 5, 6, 8, 10, 12, 13 and TNFα were markedly elevated. However, HMGB-1 and sRAGE were unaffected. No difference between placebo/GC and iNO/GC treatment was observed in the clinical or cytokine response, neither was there any difference between the first and the second exposure to endotoxin. CONCLUSIONS: pre-treatment with iNO 80 p.p.m. along with GC (2mg/kg) administrated after the endotoxin challenge could not modulate the systemic inflammatory response in this model of human experimental inflammation.

Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosis.

AIM: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. We hypothesized that those piglets exposed to prolonged iNO react with a modified renal function. METHODS: Randomized, placebo-controlled exposure to 40 p.p.m. iNO (30 h) in piglets (n = 20). Plasma and urine were sampled during three periods (first and second 12 h periods, and finally a 6 h period). We measured urine volumes, plasma and urine electrolytes (UNa, UK, UCl), plasma creatinine and urea. We calculated creatinine clearance (Ccr), and fractional excretions of sodium and potassium (FENa, FEK) and urinary excretions of electrolytes (UENa, UEK, UECl). Haemodynamic data were recorded and renal tubular apoptosis detected. RESULTS: For the first 12 h, certain parameters significantly increased in the iNO group (mean +/- SD): UNa (mmol L(-1)), 87.7 (+/-35.0) vs. 39.3 (+/-22.9), UCl (mmol L(-1)) 80.4 (+/-32.8) vs. 48.0 (+/-26.7), FENa (%) 2.1 (+/-0.8) vs. 0.7 (+/-0.5), FEK (%) 31.7 (+/-7.0) vs. 20.7 (+/-12.3), as well as UENa (mmol) 61.0 (+/-21.1) vs. 27.6 (+/-17.9) and UECl (mmol) 57.3 (24.5) vs. 37.6 (29.0). These changes were absent in the second and third periods of the study. Significant differences in percentage of apoptotic cell nuclei in the renal cortex and medulla were found after iNO exposure: 39% vs. 15%. CONCLUSION: Exposure to 40 p.p.m. iNO in healthy anaesthetized piglets has a transient natriuretic effect that disappears after 12 h. We also found evidence of renal tubular apoptosis promotion after 30 h of iNO.

Immediate and 5-year cumulative outcome after paediatric intensive care in Sweden.

BACKGROUND: Little has been reported about intensive care of children in Sweden. The aims of this study are to (I) assess the number of admissions, types of diagnoses and length-of-stay (LOS) for all Swedish children admitted to intensive care during the years 1998-2001, and compare paediatric intensive care units (PICUs) with other intensive care units (adult ICUs) (II) assess immediate (ICU) and cumulative 5-year mortality and (III) determine the actual consumption of paediatric intensive care for the defined age group in Sweden. METHODS: Children between 6 months and 16 years of age admitted to intensive care in Sweden were included in a national multicentre, ambidirectional cohort study. In PICUs, data were also collected for infants aged 1-6 months. Survival data were retrieved from the National Files of Registration, 5 years after admission. RESULTS: Eight-thousand sixty-three admissions for a total of 6661 patients were identified, corresponding to an admission rate of 1.59/1000 children per year. Median LOS was 1 day. ICU mortality was 2.1% and cumulative 5-year mortality rate was 5.6%. Forty-four per cent of all admissions were to a PICU. CONCLUSIONS: This study has shown that Sweden has a low immediate ICU mortality, similar in adult ICU and PICU. Patients discharged alive from an ICU had a 20-fold increased mortality risk, compared with a control cohort for the 5-year period. Less than half of the paediatric patients admitted for intensive care in Sweden were cared for in a PICU. Studies are needed to evaluate whether a centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population.

A retrospective survey of outpatients with long-term tracheostomy.

BACKGROUND: The Respiratory Unit (RU) at Danderyd University Hospital opened in 1982, with the expressed goal of supporting outpatients with long-term tracheostomy. The primary aim of this retrospective study in tracheostomized patients was to compare the need for hospital care in the 2-year period before and after the tracheostomy. METHODS: Data were collected from patient medical records at the RU, from the National Board of Health and Welfare, Sweden and from the Official Statistics of Sweden. The subjects were RU patients in 1982 (Group 1, n = 27) and in 1997 (Group 2, n = 106) with long-term tracheostomy surviving at least 4 years after the tracheostomy. RESULTS: Both groups had few and unchanged needs for hospital care after tracheostomy. They spent > or = 96% of their time out of hospital. In 1997, (group 2) the number of patients, diagnoses and need for home mechanical ventilation had increased. Life expectancy was assessed for patients in Group 1. Data showed that they lived as long as an age-matched and gender-adjusted control cohort. CONCLUSIONS: Long-term tracheostomy may not increase the need for hospital care and does not reduce life expectancy. These clinical observations were made in a setting where patients had regular access to a dedicated outpatient unit.

Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers.

BACKGROUND: Roughly 400.000 cases of sepsis occur every year in the United States only and this is associated with a very high mortality. Bacterial lipopolysaccharide (LPS) triggers systemic inflammatory reactions in sepsis. However, down-stream cellular cascade initiated by LPS is still being elucidated. Nitric oxide (NO) and matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are known to be induced by LPS. We have investigated the release of NO, MMP-2 and MMP-9 following infusion of LPS to volunteers. METHODS: IPS (2 ng kg-1) was infused to 10 healthy volunteers. Before the experiments were started the subjects had an intravenous catheters placed. An electrocardiogram was also placed and monitored constantly. Body temperature was measured by ear thermometer every 10 min Venous blood was collected and cell-free plasma assayed for the presence of MMP-2 and MMP-9 using zymography and NO using HPLC assay for NO metabolites, nitrite and nitrate. RESULTS: The administration of LPS resulted in increased body temperature and tachycardia. Time-dependent release of MMP-9(30 fold increase from the baseline) peaking at 2 h following infusion of LPS was observed. LPS did not significantly modify the activity of MMP-2 (P > 0.05). Infusion of LPS did not significantly change the levels of nitrite and nitrate (from 60 +/- 11 to 67 +/- 10 micro m, P > 0.05). CONCLUSION: The release of MMP-9, but not MMP-2 or NO, is a sensitive index of endotoxaemia in humans. MMP-9 release may contribute to the pathogenesis of sepsis via its pro-inflammatory effects on the vasculature.

Delivery characteristics of a combined nitric oxide nasal continuous positive airway pressure system.

BACKGROUND: Nitric oxide (NO), when inhaled, has a synergistic effect with airway recruitment strategies such as positive endexpiratory pressure (PEEP) or continuous positive airway pressure (CPAP) in improving oxygenation in lung injury. METHODS: We modified a commercially available nasal CPAP (nCPAP) system to enable the concomitant delivery of inhaled NO (iNO) and nCPAP to neonates and term babies. Oxygen, NO and nitrogen dioxide (NO2) concentrations were measured, comparing the effects of using 50 or 1000 parts per million (p.p.m.) NO stock gas cylinders. RESULTS: Stable and accurate delivery of iNO was found for both stock gas concentrations. Using a 50 p.p.m. NO stock gas resulted in limited NO2 formation, with a maximum inspired NO2 concentration of < or = 0.3 p.p.m. (dose range up to 37 p.p.m. iNO), which was interpreted as the result of progressive dilution with nitrogen. In contrast, using a 1000 p.p.m. NO stock gas cylinder, inspired NO2 levels increased nonlinearly as expected with an increasing inspired concentration of NO. CONCLUSIONS: Inhaled NO can be safely and reliably delivered by the system we describe. The NO2 levels generated by the system are low, at least up to a dose of 37 p.p.m. NO, regardless of a stock gas concentration of 50 or 1000 p.p.m. NO. Using a 50 p.p.m. NO stock gas concentration, up to 80% oxygen can be given at 10 p.p.m. iNO.

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.

[Ventilation in ARDS: respirator, prone position, NO or artificial lung]. / Ventilation vid ARDS: respirator, bukläge, NO eller konstgjord lunga?

This review discusses the treatment of impaired gas exchange in acute respiratory distress syndrome (ARDS) using conventional ventilation, the open lung approach, prone position, nitric oxide (NO) inhalation and extracorporeal membrane oxygenation (ECMO). It is concluded that ventilation with high inspiratory pressures or volumes should be avoided, and that the open lung approach should be used as the first step. If this does not lead to satisfactory results, prone positioning is recommended, and if life-threatening hypoxemia persists, ECMO could be considered. NO inhalation is not recommended.

Inhaled nitric oxide does not influence bleeding time or platelet function in healthy volunteers.

BACKGROUND: Bleeding time has been reported to increase during gaseous nitric oxide (NO) inhalation in healthy volunteers and patients, and it has been speculated that inhaled NO inhibits platelet function. However, results have not been unanimous, and we have been unable to document any effects of inhaled NO on circulating platelets. MATERIALS AND METHODS: We performed a double-blind, placebo controlled cross-over study in which healthy volunteers (n = 15) inhaled NO (30 ppm, 30 min) or control gas. Aspirin (640 mg x 1 orally) was used as positive control on the third occasion (n = 14). Bleeding time was measured, and platelet function was determined flow cytometrically by measuring the expression of P-selectin on circulating platelets and locally activated platelets in wound blood. Skin perfusion close to the site for bleeding time incisions was assessed by laser Doppler flowmetry. RESULTS: Bleeding time was unaffected by NO, as there were slight increases during both NO and control inhalation (+20% and +14% respectively, P = 0.9). Similarly, NO inhalation had no effect on platelet P-selectin expression in either systemic or wound blood, or on skin perfusion. Aspirin pretreatment, on the other hand, prolonged bleeding time (P < 0.001) and decreased P-selectin expression of platelets in wound blood (P = 0.03). CONCLUSIONS: This first placebo-controlled study indicates that inhaled NO does not influence either bleeding time, platelet activity or skin perfusion. Thus, it is unlikely that treatment of critically ill patients with inhaled NO will aggravate haemostatic disturbances, which has previously been feared, by influencing platelet function.

Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide.

OBJECTIVE: To determine whether inhalation of nitric oxide (INO) can increase the frequency of reversal of acute lung injury (ALI) in nitric oxide (NO) responders. DESIGN: Prospective, open, randomised, multicentre, parallel group phase III trial. SETTING: General ICUs in 43 university and regional hospitals in Europe. PATIENTS: Two hundred and sixty-eight adult patients with early ALI. INTERVENTIONS: NO responders were patients whose PaO(2) increased by more than 20 % when receiving 0, 2, 10 and 40 ppm of INO for 10 min within 96 h of study entry. Responders were randomly allocated to conventional treatment with or without INO. INO, 1-40 ppm, was given at the lowest effective dose for up to 30 days or until an end point was reached. The primary end point was reversal of ALI. Clinical outcome parameters and safety were assessed in all patients. RESULTS: Two hundred and sixty-eight patients were recruited, of which 180 were randomised NO responders. Frequency of reversal of ALI was no different in INO patients (61 %) and controls (54 %; p > 0.2). Development of severe respiratory failure was lower in the INO (2.2 % ) than controls (10.3 %; p < 0.05). The mortality at 30 days was 44 % for INO patients, 40 % for control patients (p > 0.2 vs INO) and 45 % in non-responders. CONCLUSIONS: Improvement of oxygenation by INO did not increase the frequency of reversal of ALI. Use of inhaled NO in early ALI did not alter mortality although it did reduce the frequency of severe respiratory failure in patients developing severe hypoxaemia.

Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers.

Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by N(G)-monomethyl-L-arginine (L-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, L-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of L-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma beta-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin-antithrombin complexes) in plasma, and bleeding time. L-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P<0.001). Neither L-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma beta-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by L-NMMA compared with placebo, but was increased by approximately 25% during NO inhalation (P<0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.

Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group.

To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were assessed between October 6th and November 30th, 1997 in 132 of 150 ICUs with resources to treat patients with intubation and mechanical ventilation (I + MV) >/= 24 h. ARF was defined as I + MV >/= 24 h. ALI and ARDS were defined using criteria recommended by the American-European Consensus Conference on ARDS. Calculation to correct the incidence for unidentified subjects from nonparticipating ICUs was made. No correction for in- or out-migration from the study area was possible. The population in the three countries >/= 15 yr of age was 11.74 million. One thousand two hundred thirty-one ARF patients were included, 287 ALI and 221 ARDS patients were identified. The incidences were for ARF 77.6, for ALI 17.9, and for ARDS 13.5 patients per 100,000/yr. Ninety-day mortality was 41.0% for ARF, including ALI and ARDS patients, 42.2% for ALI not fulfilling ARDS criteria, and 41.2% for ARDS.

Formation of nitrogen dioxide from nitric oxide and their measurement in clinically relevant circumstances.

Therapy with inhaled nitric oxide in oxygen requires adequate monitoring of nitric oxide and nitrogen dioxide. The characteristics of chemiluminescence and electrochemical measurement techniques were determined by analysis of continuously flowing gas mixtures and comparisons with traceable gas standards. Gas mixtures were also diluted with mass flow controllers and in addition created in ventilator breathing systems. Factors influencing the formation of nitrogen dioxide were defined. Both techniques accurately measured nitric oxide (10-80 parts per million, ppm) and nitrogen dioxide (0.5-5 ppm) in normoxic and hyperoxic (90% oxygen) gas in the studied ranges. Nitrogen dioxide in hyperoxic gas had three origins: (1) from the premixing point of nitric oxide in nitrogen, (2) as a result of the mixing process, and (3) from post-mixing and time-dependent continuous formation of nitrogen dioxide in oxygen. We conclude that adequate monitoring is possible and that factors affecting nitrogen dioxide generation can be defined.

Induction of chromosome aberrations in peripheral blood lymphocytes after short time inhalation of nitric oxide.

INTRODUCTION: inhalation of nitric oxide (INO) leads to vasodilation of pulmonary vasculature in ventilated regions of the lung. The clinical use of INO, although not formally approved as a drug, is widespread. NO may rapidly form nitrogen dioxide (NO2) in an oxygen containing gas mixture. NO2 has been shown to induce chromosome aberrations and mutations in both animal and bacterial test systems. We investigated whether a 2-h exposure to NO would increase frequencies of cells with chromosome aberrations in peripheral blood lymphocytes of human volunteers. METHODS: 10 volunteers were exposed to inhaled NO 40 parts per million (ppm) for 2 h. Pre- and post-exposure blood samples were analysed. RESULTS: no statistically significant differences (p

Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide.

We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.

Pulmonary function in adult survivors of severe acute lung injury treated with inhaled nitric oxide.

BACKGROUND: Following an episode of acute respiratory distress syndrome (ARDS), some degree of measurable pulmonary impairment may be anticipated. ARDS is thought to be the more severe form of acute lung injury (ALI) and a recently proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide (INO). We carried out a non-randomised follow-up study with pulmonary function tests on survivors of severe ALI/ARDS treated with INO. METHODS: Sixteen previously healthy pulmonary patients, survivors of severe ALI/ARDS, were evaluated with pulmonary function tests >8 months after the acute event. The tests included static and dynamic spirometry, diffusion capacity for carbon monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph. RESULTS: The most common abnormality seen was a low DLCO in 69% of the patients. Abnormally low values were seen in forced vital capacity in 31%, in forced expiratory volume in 1 s in 13%, and in residual volume and total lung capacity in 6%. Blood gas data were within normal limits in 15/16 patients. All chest radiographs showed resolution of the interstitial and alveolar changes present during the acute event. CONCLUSION: In this non-randomised follow-up study we conclude that a degree of measurable pulmonary impairment after INO treatment in severe ALI/ARDS was common, but did not differ markedly from other published studies on pulmonary function in similar patient material. No late unexpected major abnormalities due to the inhaled nitric oxide treatment could be identified in these survivors.