Adult respiratory distress syndrome, Pathophysiology and inflammatory mediators in bronchoalveolar lavage.
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Bronchoalveolar Lavage Fluid↗
Biomedical subjects
J Modig
Publications and source records attributed to J Modig.
Beneficial effects on intraoperative and postoperative blood loss in total hip replacement when performed under lumbar epidural anesthesia. An explanatory study.
The effects of continuous lumbar epidural anesthesia and two types of general anesthesia on blood loss and hemodynamics during and after total hip replacement were compared in three groups of patients. Fourteen patients received local anesthetics via continuous lumbar epidural administration; 10 patients received inhalational anesthetics and breathed spontaneously after endotracheal intubation; and 14 received artificial ventilation after intubation and intermittent intravenous (i.v.) injections of pancuronium and fentanyl. The results documented that both intraoperative and postoperative blood losses were significantly reduced in patients subjected to total hip replacement under lumbar epidural anesthesia as compared with the patients receiving the two general anesthetic techniques. Hemodynamic differences explained the differences in blood loss. The epidural anesthesia induced hypotension on the arterial and venous sides as compared with the two general anesthetic techniques. Inhalational anesthesia also induced hypotension on the arterial and venous sides intraoperatively as compared with general anesthesia with artificial ventilation. Postoperatively, the hemodynamics of the general anesthesia groups were similar, and no differences in blood loss occurred. Continuous' epidural anesthesia can be viewed as a tool to achieve hypotensive anesthesia--notably on the venous side--for the purpose of minimizing blood loss. The reduction in blood loss associated with lumbar epidural anesthesia is beneficial in decreasing the hazard and cost of blood transfusion.
Aged↗
Beneficial effects of dextran 70 versus Ringer's acetate on pulmonary function, hemodynamics and survival in a porcine endotoxin shock model.
The effects of Dextran 70 with NaCl as against Ringer's acetate on hemodynamics, gas exchange, oxygen transport and survival were evaluated in a porcine model of pulmonary and circulatory insufficiency induced by a continuous i.v. endotoxin infusion over 6 h. Dextran and Ringer's acetate were infused continuously to maintain baseline mean left atrial pressure (MLAP) throughout the endotoxin period. Twelve pigs receiving endotoxin + Ringer's acetate displayed a progressive 45% decline in cardiac output (Qt) and a two peaked increase in pulmonary vascular resistance (PVR) with a late increase of 250%. Venous admixture (Qva/Qt) increased progressively more than 6-fold and extravascular lung water (EVLW) increased by 55%. Mean arterial blood pressure (MAP) fell by 25%, oxygen delivery by 40%, base excess (BE) ranged between - 4.5 and - 9 mmol.1(-1) at the end of the endotoxin period and 4 of 12 animals died. Polymorphonuclear cell count (PMNs) fell rapidly by 90% and was severely decreased throughout the endotoxin period. Contrastingly, the 12 pigs that received endotoxin + Dextran maintained Qt near baseline and PVR was significantly lower in this group. Qva/Qt increased progressively more than 4-fold, but was significantly lower than in the Ringer's group as was the increase in EVLW (23%). MAP only decreased by 10%, oxygen delivery only decreased by 20%. BE ranged between - 1.0 and - 3.0 at the end of the endotoxin period and all animals survived. PMNs fell by 90% at 0.5 h but subsequently tended to return towards baseline. PMNs were significantly increased compared with the Ringer's group. The amount of Ringer's acetate necessary to maintain a stable MLAP averaged 4.6 times the Dextran volume. The superiority of Dextran as compared with Ringer's acetate in this endotoxemic shock model seems to be consequent to better rheological effects combined with pharmacological interactions with granulocytes.
Animals↗
Comparison of effects of dextran-70 and Ringer's acetate on pulmonary function, hemodynamics, and survival in experimental septic shock.
The effects of dextran-70 with NaCl vs. Ringer's acetate on hemodynamics, gas exchange, oxygen transport, and survival were evaluated in a porcine model of pulmonary and circulatory insufficiency induced by a continuous iv endotoxin infusion over 6 h. Dextran and Ringer's acetate were infused continuously to maintain baseline mean left atrial pressure (LAP) throughout the endotoxin period. Twelve pigs receiving endotoxin + Ringer's acetate displayed a progressive 45% decline in cardiac output (Qt) and a two-peaked increase in pulmonary vascular resistance (PVR) with a late increase of 250%. Venous admixture (Qva/Qt) increased progressively more than six-fold and extravascular lung water (EVLW) increased by 55%. Mean arterial BP (MAP) fell by 25%, oxygen delivery by 40%, base excess (BE) ranged between -4.5 and -9 mmol/L at the end of the endotoxin period and four of 12 animals died. Polymorphonuclear cell count (PMN) fell rapidly by 90% and was decreased severely throughout the endotoxin period. By contrast, the 12 pigs that received endotoxin + dextran maintained Qt near baseline and PVR was significantly lower in this group. Qva/Qt increased progressively more than four-fold, but it was significantly lower than in the Ringer's acetate group as was the increase in EVLW (23%). MAP only decreased by 10%, oxygen delivery only decreased by 20%. BE ranged between -1.0 and -3.0 mmol/L at the end of the endotoxin period and all animals survived. PMN fell by 90% at 0.5 h but subsequently tended to return toward baseline, and PMN were significantly increased compared with the Ringer's acetate group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regional anaesthesia and blood loss.
Epidural and spinal anaesthesia for various types of surgery offer advantages over general anaesthesia by decreasing blood loss and transfusion requirements. This paper focuses on the importance of the choice of anaesthesia on surgical blood loss in total hip arthroplasty. Haemodynamic differences, with lower arterial blood pressure, lower central venous blood pressure, and most importantly lower peripheral venous blood pressure in the surgical wound seem to explain the lower blood loss intra- and post-operatively in patients given regional anaesthesia. These differences in haemodynamics give rise to less arterial, and notably less venous oozing of blood from the surgical area. The latter observation is strengthened by the significant correlations between the intraoperative peripheral venous blood pressure and the intraoperative blood loss. The reduction in blood loss and consequently the reduced transfusion requirements in regional anaesthesia are beneficial in decreasing the hazards and costs of homologous blood transfusion. Although impossible to quantify, reduced bleeding also greatly facilitates the surgeon's work.
Anesthesia, Conduction↗
Indications of chlormethiazole as a protective agent in experimental endotoxemia.
Chlormethiazole, which is derived from the thiazole moiety of thiamine, possesses sedative, hypnotic and anticonvulsant properties. This anesthetic agent was compared with ketamine in a porcine model of endotoxemia to evaluate effects on cardiovascular and pulmonary function, oxygen delivery and survival. Continuous 6-hour intravenous infusion of Escherichia coli endotoxin caused pronounced pulmonary and cardiovascular derangement and decreases in oxygen delivery and pH in 13 pigs given ketamine anesthesia. Eight of thirteen pigs survived the observation period. Contrastingly, 10 pigs given chlormethiazole anesthesia and endotoxin showed a significantly attenuated response. Thus, the increases in mean pulmonary arterial pressure, venous admixture and extravascular lung water were significantly lower and the decreases in cardiac output, oxygen delivery and pH were significantly modified by chlormethiazole. All 10 pigs survived the observation period. Chlormethiazole may increase the clearance of endotoxin and thus ameliorate the endotoxin response. Although extrapolating from animal data requires great caution, these data may favor the use of chlormethiazole in septic states requiring surgical intervention and anesthesia and as sedation in critically ill septic patients in our intensive care units.
Animals↗
Haematological, physiological and survival data in a porcine model of adult respiratory distress syndrome induced by endotoxaemia. Effects of treatment with N-acetylcysteine.
The effects of N-acetylcysteine (NAC)--which is supposed to act as a free radical scavenger--were evaluated on lung function, haemodynamics and oxygen transport in a porcine model of pulmonary and cardiovascular failure induced by endotoxaemia. Three pigs, serving as controls, received NAC without endotoxin (E) for 6 h, and no notable physiological changes were found. Five pigs received a continuous infusion of E alone for 6 h and displayed a 90% decrease in leukocyte count and a 66% decrease in platelet count. Physiologically a four-fold increase in venous admixture (Qva/Qt), a nearly 2-3 fold increase in mean pulmonary arterial pressure (MPAP) and a progressive decline in cardiac output (Qt) of 60% were documented. Extravascular lung water (EVLW) increased 66%, mean arterial pressure (MAP) decreased 46% and oxygen delivery decreased 52%, leading to a metabolic acidosis. Three animals died during the observation period. Contrastingly, eight pigs, pretreated with NAC 150 mg.kg-1 which was continued at 20 mg.kg-1.h-1, showed a significantly attenuated response to E. Thus, leukocyte and platelet counts decreased 70% and 48%, respectively. Physiologically Qva/Qt increased 2.5-3 fold, MPAP increased 1.3-2 fold, and Qt decreased 32%. EVLW increased 27%, MAP decreased 27% and oxygen delivery decreased only 33% which kept the pH in the normal range. All animals survived the observation period, a significant difference from the E alone group. Thus, NAC significantly attenuated all monitored haematological and pathophysiological changes in the endotoxin model of ARDS in pigs. In addition to a reported free radical scavenger effect of NAC, our results support the assumption that NAC may counteract leukocyte and platelet aggregation in the lung thereby contributing to the beneficial outcome.
Acetylcysteine↗
Prevention by granulocyte depletion of endotoxin-induced adult respiratory distress syndrome. An experimental study in pigs.
To see whether circulating granulocytes are of importance in mediating endotoxin-induced pulmonary failure with similar characteristics to the human adult respiratory distress syndrome (ARDS), we made pigs granulocytopenic by injecting hydroxyurea via a central venous line for 10 days. The circulating granulocyte count decreased by 95% prior to the start of the continuous (6 h) endotoxin infusion (n = 8), whereas pigs sham-infused for 10 days had a normal granulocyte count before starting the continuous endotoxin infusion (n = 8). Four granulocyte depleted pigs served as controls and received physiological saline instead of endotoxin. No physiological changes occurred in controls during the observation period of 6 h and all animals survived. Granulocyte depletion in response to endotoxin was associated with significantly attenuated pulmonary hypertension, significantly better preservation of cardiac output, significantly better maintained arterial oxygenation and a significantly smaller increase in extravascular lung water throughout the observation period as compared with non-granulocytopenic animals. Seven out of 8 granulocytopenic animals survived the observation period as against 4 out of 8 in non-granulocytopenic animals. Although one should be extremely careful in applying experimental results to the clinical situation, our findings might support the potential use of agents which interfere with granulocyte activation in septic-induced ARDS.
Agranulocytosis↗
Complement activation and increased alveolar-capillary permeability after major surgery and in adult respiratory distress syndrome.
The concentrations of C3a des Arg were measured in bronchoalveolar fluid (BAL) and plasma from 12 patients with adult respiratory distress syndrome (ARDS). Compared with 32 controls, all patients had increased BAL fluid levels (p less than .001), and nine of 12 had increased plasma levels (p less than .001) of this split product from the third complement component. Reduced total hemolytic activity (CH50) in serum was seen in five patients (p less than .01). As an indication of damage to the alveolar-capillary barrier, ten of the 12 ARDS patients had elevated albumin concentrations in BAL fluid (p less than .001). These signs of complement activation and lung tissue damage are not specific for ARDS. Thus, in 15 patients investigated preoperatively and postoperatively, we found that major surgery induced a significant increase of BAL fluid C3a (p less than .01) and plasma C3a (p less than .02), a significant reduction of CH50 (p less than .001), and a significant increase of BAL fluid albumin (p less than .02). Similar values of CH50 and plasma C3a were seen in ARDS and after surgery (p greater than .05). Of the 12 ARDS patients, eight had increased BAL fluid concentrations of C3a (p less than .001), and ten had increased BAL fluid levels of albumin (p less than .001) compared with the post-surgical patients. Measuring complement consumption in blood by these techniques is of limited value in ARDS due to the lack of specificity. BAL fluid albumin has a similar degree of sensitivity and specificity for ARDS as does BAL fluid C3a.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Intermittent and continuous positive-pressure ventilation in the prophylaxis of endotoxin-induced lung insufficiency. A study in pigs.
The effects of intermittent and continuous positive-pressure ventilation (IPPV and CPPV) instituted prophylactically were evaluated in a porcine model of endotoxin-induced pulmonary and cardiovascular failure. Pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin over 6 h. Twenty animals, breathing air spontaneously, received endotoxin without treatment. Fifteen animals were treated prophylactically with IPPV (normoventilation with air). Nine animals received prophylactic treatment with CPPV (positive end-expiratory pressure 0.8 kPa (8 cmH2O). Endotoxin infusion in spontaneously breathing animals caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in extravascular lung water (EVLW). Cardiac output (Qt) and O2 delivery decreased considerably. Metabolic acidosis indicated oxygen deficit. Eleven of 20 animals died during the observation period. IPPV improved arterial oxygenation during endotoxin infusion, and the increase in EVLW tended to be lower. The alterations in pulmonary haemodynamics, Qt and O2 delivery, were of the same magnitude as in spontaneously breathing animals. Survival was improved. CPPV fully prevented the deterioration in pulmonary gas exchange and the development of pulmonary oedema. There was an accentuated increase in PVR. Qt and O2 delivery decreased markedly and a severe metabolic acidosis developed. All animals treated with CPPV died during the observation period. These results indicate that prophylactic IPPV and CPPV may counteract the development of sepsis-induced lung insufficiency in man. However, it must be emphasized that adequate cardiovascular support is essential in optimizing the treatment.
Animals↗
Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome.
The concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients with adult respiratory distress syndrome (ARDS). The mean level was 163 +/- 85 (SD) micrograms/L and significantly increased (p less than 0.001) compared with the levels in control subjects (19 +/- 18 micrograms/L). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in ARDS, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. No relation was seen between BAL fluid ECP or MPO and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS. Lavage ECP levels correlated strongly with the severity of lung damage defined by pulmonary oxygenation index (PaO2/inspired fraction of O2). Activation of eosinophils, neutrophils, and the complement system is not specific for ARDS but was also observed in patients after major surgery, but at a significantly lower level (p less than 0.001). It is concluded that eosinophil activation is part of the inflammatory process in the lung in ARDS. The association observed between elevated lavage fluid levels of ECP and reduced pulmonary function in ARDS might reflect a pathophysiologic role for ECP and other cytotoxic eosinophil products in this syndrome and should be evaluated.
Adult↗
Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model.
Pulmonary and cardiovascular function, oxygen delivery and mortality were compared in endotoxemic pigs spontaneously breathing air and with continuous i.v. infusion of ketamine anesthesia (n = 10) or the equianesthetic dose of metomidate (n = 10). Continuous 6-hour i.v. infusion of endotoxin caused profound pulmonary and cardiovascular derangement in both groups. Cardiac output, mean arterial blood pressure, oxygen delivery and base excess were significantly higher and pulmonary vascular resistance significantly lower from 2-3 hours onwards in the ketamine than in the metomidate group. Six-hour survival was 6/10 and 1/10 in the respective groups. Death was presumably due to insufficient oxygen delivery in relation to tissue demand, reflected in the metomidate group's low base excess values. Control, non-stressed pigs showed no notable physiologic changes with either anesthetic regimen. The study demonstrated the importance of the type of anesthesia in stressful endotoxemic animal models. Although extrapolation of animal data requires great caution, the results may favor use of ketamine over etomidate (the clinical analogue of metomidate) in septic shock states requiring surgical intervention.
Anesthesia, Intravenous↗
Volume substitution and treatment with prostaglandin E1 in a porcine model of endotoxaemia-induced pulmonary and cardiovascular failure.
The effects of prostaglandin E1 (PGE1) and volume substitution (5% albumin) on pulmonary haemodynamics and oxygen transport were evaluated in a porcine model of pulmonary and cardiovascular failure. Albumin was infused i.v. to maintain baseline mean left atrial pressure throughout the experiments. Ten pigs received endotoxin + albumin and showed ten-fold increase in venous admixture, 90% increased extravascular lung water and 25% fall in cardiac output. Oxygen delivery and base excess decreased significantly and four pigs died. In ten other endotoxin-albumin-treated pigs PGE1 infusion (0.25 micrograms X kg-1 X min-1) was begun after established pulmonary and cardiovascular dysfunction, for closer mimicking of clinical use. The raised pulmonary vascular resistance thereafter normalized and extravascular lung water increased by only 15%, but the increase in venous admixture was not influenced. Cardiac output was maintained at baseline. PGE1 prevented further derangement of oxygen delivery and base excess. All the animals survived. The clinical implications may be that volume infusion, even optimally titrated, is not optimum treatment in endotoxemic pulmonary and cardiovascular failure. PGE1 added to optimum volume treatment may be a useful adjuvant in endotoxaemia.
Albumins↗
Intra- and post-operative blood loss and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia.
The effects of lumbar epidural anaesthesia and two types of general anaesthesia on blood loss and haemodynamics during and after hip replacement were compared in three groups of patients. One group (n = 14) received continuous lumbar epidural anaesthesia, another group (n = 10) was given inhalational anaesthesia and spontaneous breathing after endotracheal intubation, and the third group (n = 14) received artificial ventilation after intubation and pancuronium and fentanyl intermittently i.v. Intra-operative blood loss in patients under epidural anaesthesia was 950 +/- 300 ml (mean +/- SD) and blood loss during the following 24 h-i.e. as long as the epidural anaesthesia was maintained-was 370 +/- 80 ml. These figures were significantly lower than the intra- and post-operative blood losses in patients under general anaesthesia with narcotics as post-operative pain treatment: 1140 +/- 200 ml (inhalational anaesthesia) followed by 480 +/- 70 ml and 1540 +/- 340 ml (artificial ventilation) followed by 500 +/- 110 ml. The intra-operative blood loss in the general anaesthesia group with spontaneous breathing was significantly smaller than the blood loss in the artificially ventilated group, whereas the post-operative blood loss in the two general anaesthetic groups was similar. Haemodynamic differences explain these differences in blood loss. Thus epidural anaesthesia induced hypotension on the arterial and venous sides. Intra-operatively, inhalational anaesthesia also induced hypotension on the arterial and venous sides compared with general anaesthesia using artificial ventilation. Post-operatively, the general anaesthesia groups behaved haemodynamically similarly and no differences in blood loss were seen. The reduction in blood loss, notably associated with lumbar epidural anaesthesia, is beneficial in decreasing the hazard and cost of blood transfusion.
Aged↗
Pathophysiologic significance of lung granulocytes in human adult respiratory distress syndrome induced by septic or traumatic shock.
To evaluate the significance of lung granulocytes in the adult respiratory distress syndrome (ARDS), 12 ARDS patients were studied with bronchoalveolar lavage (BAL) within 4-12 hours after clinical diagnosis of the syndrome. The specificity of pulmonary granulocytes in ARDS was investigated in comparison with five patients requiring ventilator treatment for cardiogenic pulmonary oedema and 17 normal patients about to undergo cholecystectomy. The percentage of granulocytes among recovered BAL cells was significantly higher in ARDS (77 +/- 18, M +/- SD) than in the cardiac (7 +/- 4) or the normal (1.5 +/- 1.0) group. In serial BAL (48-hour intervals) in five ARDS patients, significant reduction of granulocytes 86 +/- 11----32 +/- 10%) accompanied clinical improvement. The percentage of granulocyte in BAL correlated significantly and inversely with the PaO2/FiO2 ratio (r = -0.98), and in ARDS it was significantly higher after septic than after traumatic shock (89 +/- 14 vs. 55 +/- 12). Myeloperoxidase, a specific constituent of neutrophils, was significantly and inversely correlated with PaO2/FiO2 ratio (r = -0.62). The findings suggest a role for activated granulocytes in the lung, with release of tissue-damaging substances, in initial ARDS pathogenesis, notably when the syndrome is sepsis-induced.
Adolescent↗
Specific coagulation and fibrinolysis tests as biochemical markers in traumatic-induced adult respiratory distress syndrome.
There is a great demand for more specific methods for assaying individual components of coagulation and fibrinolysis, with the chief aim being to use them as biochemical markers of the Adult Respiratory Distress Syndrome (ARDS) induced by severe trauma. This prospective study was undertaken on 18 severely traumatized patients in various stages of shock admitted to the Intensive Care Unit of the University Hospital in Uppsala, Sweden. After haemodynamic restitution, during which surgery was often required as an intervening procedure, the patients were carefully studied regarding pulmonary function, coagulation and fibrinolysis. Eight patients developed ARDS according to our criteria, and one patient died from this condition. It was found that patients who developed ARDS had significantly lower levels of antithrombin-III, higher levels of von Willebrand factor levels, higher levels of tissue plasminogen activator inhibitors and lower levels of plasminogen as compared with those who did not develop this condition. We believe that these coagulation and fibrinolysis variables can be used along with appropriate pulmonary function tests as specific biochemical markers to disclose the development of traumatic-induced ARDS.
Adolescent↗
Biochemical markers in a porcine model of adult respiratory distress syndrome induced by endotoxemia.
To evaluate the influence of a continuous endotoxin infusion on different hematological and biochemical variables which might underlie endotoxin-induced ARDS we investigated 2 groups of pigs, one with and one without endotoxin. Complement activation - both via the classical and alternative pathways -- antithrombin III, (AI-III) factor VIII-related antigen and fibronectin levels could not precisely predict the development of ARDS in the individual animal. It was found, however, that the animals which reacted with a severe endotoxin-induced pulmonary dysfunction (pulmonary responders) had significantly higher levels of complement of both the classical and alternative pathways, greater concentrations of AT-III and factor VIII-related antigen and higher fibronectin levels. These findings might probably be explained by a greater reactivity, i.e. synthesis and release, of these biochemical components in the animals which responded with a severe pulmonary reaction, a phenomenon which probably concealed the consumption. A greater "reactivity" regarding the drop in polymorphonuclear cell count was found in pulmonary responders; a phenomenon which, however, was not compensated for by increased production. A finding of presumably great clinical importance was that animals surviving the observation period had significantly higher levels of fibronectin already at baseline and throughout the observation period.
Animals↗
Lethal adult respiratory distress syndrome after meningococcal septicemia biochemical markers in bronchoalveolar lavage.
A lethal case of Adult Respiratory Distress Syndrome (ARDS) consequent to meningococcal septicemia is clinically and physiologically described. Very high levels of eosinophil cationic protein and lactoferrin in bronchoalveolar lavage were observed in spite of peripheral eosinopenia and neutropenia. These findings provide support for the hypothesis that activated granulocytes are involved in the pathogenesis of septic-induced ARDS.
Adolescent↗