Background Brain activation resulting from acute postoperative pain has to our knowledge not previously been studied using positron emission tomography, except from one case study. The aim of this study was to monitor activation in brain sensory pathways during acute pain after surgery of the hand. A secondary aim was to compare brain activation in clinical postoperative pain to that previously reported, by the same research group, for a model of experimental pain from the same body area. Increase in regional cerebral blood flow (rCBF) is presumed to indicate neuronal activation and decrease in blood flow decreased neuronal firing. An increase in blood flow in a brain region may represent stimulatory activity as well as inhibitory. Methods Brain activity was measured during clinical postoperative pain and a pain free state in six patients with positron emission tomography (PET) as changes in regional cerebral blood flow (rCBF). rCBF during pain from surgery of the right thumb base was compared with a pain free state achieved by regional anaesthesia of the painful area. Results In postoperative pain, patients had a significantly higher CBF in the contralateral/primary and secondary somatosensory cortices as well as in the contralateral motor cortex compared to the pain free stat during local regional anaesthesia. Relatively lower rCBF during the pain state was observed in clusters in the contralateral tertiary sensory cortex, ipsilateral and contralateral secondary visual cortex, prelimbic cortex, ipsilateral prefrontal as well as anterior cingulate cortex and contralateral secondary somatosensory cortex. The increased rCBF in primary and somatosensory cortices probably correspond to pain localizing processing. We also compared the findings in cerebral activation patterns of the postoperative pain state as described above, with the results from a previously published study by the same research group, using an experimental pain model when pain was inflicted with application of mustard oil in the same location, the thumb base region of the right hand. Since no formal statistical analysis was carried out between the two studies, the data are not very strong, but the differences reported were obvious when comparing the two situations. The comparison gave the following outcome: Digit activation occurred in identical sensory brain areas, i.e. primary and secondary somatosensory cortices, as compared to the changes in this study, supporting that pain localization processes use similar sensory pathways in a nociceptive acute experimental pain model, and in clinical acute postoperative nociceptive pain. Dissimilarities were observed between the models in activation of brain areas coding of the emotional pain qualities, indicating some differences between the experimental and "real" acute nociceptive pain. Conclusion We have reported a distinct cerebral activation pattern produced by acute postoperative pain following hand surgery. The findings were compared to data obtained in a previously published report of the cerebral activation pattern from an acute experimental pain model in volunteers. We found similarities as well as some differences in the activation pattern between the two situations.

The effects of Ringer's acetate, 6% dextran-70, 7.5% NaCl, and the combination of 7.5% NaCl and dextran-70 were tested in resuscitation from endotoxin shock induced by continuous iv infusion of Escherichia coli endotoxin in pigs. After about 3 h, a reproducible shock state was achieved and treatment was started, governed by the left atrial pressure. The hypertonic solutions (7.5% NaCl and 7.5% NaCl in dextran-70) did not show any overall advantages over the isotonic solutions (Ringer's acetate and dextran-70). Only transient beneficial hemodynamic effects lasting less than 30 min after infusion were seen. When dextran-70 was administered, cardiovascular function was markedly improved and oxygen delivery (DO2) and survival were significantly higher compared with the crystalloid groups (Ringer's acetate and 7.5% NaCl). Administration of large amounts of Ringer's acetate resulted in an immediate deterioration of pulmonary function. It was difficult to elevate left atrial pressure or even to keep it at baseline level, and cardiac index was only transiently increased. The overall result was a deterioration of DO2 and poor survival compared with the dextran-70 treated pigs. We conclude that dextran-70 is superior to Ringer's acetate in resuscitation from endotoxin-induced shock in pigs. Furthermore, we found no role for the use of hypertonic saline, alone or in combination with dextran, in the treatment of this type of prolonged endotoxin shock.

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.

Using the multiple inert gas elimination technique, ventilation/perfusion (V/Q) relationships were studied in an experimental porcine model of the early Adult Respiratory Distress Syndrome (ARDS) to establish the nature of the increased venous admixture. Six animals served as controls and revealed no major changes apart from a 10% decrease in cardiac output during the 4‐h observation period. All control animals showed a shift to a higher mean V/Q of perfusion (Q mean ) and a maintained log standard deviation (Q sd ) throughout the experiment. The distribution was unimodal and centered around a V/Q ratio of 1.0. The share of perfusion to V/Q ratio < 0.005 (i.e. true shunt, Q) remained unchanged at 6–7% of cardiac output. Nine animals, given a continuous infusion of E. coil endotoxin, showed a significant decrease of 53% in cardiac output (Q) at 4 h. Mean pulmonary artery pressure (MPAP) showed a 2‐phase reaction with a peak level at 0.5 h, and a second gradual increase from 2 h onwards. Venous admixture doubled at 0.5 h, after which it declined but remained elevated throughout the observation period. All endotoxin animals showed a shift in perfusion to a higher Q mean with a significantly wider Q sd at 0.5, 2 and 4 h. The distribution was unimodal and centered around a V/Q ratio of 1.0. True shunt was unchanged at 6–7% of cardiac output throughout the study. The increase in venous admixture in this experimental ARDS model is consequently explained by the widening of the V/Q scatter and is due to a perfusion shift to lower ventilation/perfusion ratios rather than to an increase in true shunt.

Studies have shown that lumbar epidural and spinal anesthesia seem to offer two distinct clinical advantages over general anesthesia, particularly in total hip replacement patients. These major regional blocks reduce the frequency of deep vein thrombosis and pulmonary embolism and reduce intraoperative and postoperative blood losses. The beneficial effects on thromboembolism are probably explained by several factors, such as hyperkinetic blood flow in the lower legs, reduced tendency to coagulation, and improved fibrinolytic function. The effects of local anesthetics on leukocytes, platelets, erythrocytes, and plasma proteins and on the interactions among various blood cells and endothelial cells are other factors in the protection against thromboembolism. Sympathicomimetic agents (i.e., epinephrine in the local anesthetic solution together with ephedrine given prophylactically to maintain a stable blood pressure) probably also play a significant role, notably on fibrinolytic function. The reduction in blood loss and thus in transfusion requirements may also be important.

Continuous non-invasive monitoring of conjunctival oxygen tension (PcjO2) versus ‘conventional’ invasive hemodynamic and oxygen transport variables was evaluated in a porcine model of septic shock induced by a continuous i.v. infusion of E.coli endotoxin over 2 hours. Seventeen pigs under ketamine anesthesia and breathing air spontaneously were investigated. PcjO2, which reflects local oxygen tension at tissue level, correlated significantly at baseline and throughout the septic course with mixed venous oxygen saturation and oxygen utilization coefficient. All these correlations were significant at the 1% level. The corresponding correlations between PcjO2 and cardiac output were significant at the 5% level. A finding of great importance was that changes in PcjO2 preceded major changes in the intermittently measured physiological variables such as SvO2 and cardiac output.

In a prospective investigation of 19 patients with traumatic (n = 11) and septic (n = 8) shock admitted to the Intensive Care Unit of the University Hospital of Uppsala, differences in coagulation and fibrinolysis between the two conditions were evaluated. It was found that plasma coagulation variables such as thrombotest, normotest and antithrombin III were significantly lower in the septic patients, thus indicating a more intense and/or altered intravascular coagulation. Significantly higher levels of the von Willerbrand factor were found in septic patients, indicating a greater release from endothelial cells and platelets. The plasminogen activator inhibitor and the plasminogen-binding form of alpha 2-antiplasmin showed significantly higher values in septic patients, indicating a greater fibrinolysis inhibition in these patients. The greater disturbance in the protease-inhibitor balance in septicaemia was also verified by significantly lower levels of plasminogen and alpha 2-macroglobulin than after traumatic shock. Two out of 11 patients in traumatic shock developed the adult respiratory distress syndrome with a slow onset and benign course, whereas six out of eight septic shock patients developed a similar syndrome with a rapid onset and malignant course. These laboratory and clinical results lend further support to the hypothesis that the differences in coagulation and fibrinolysis systems reflect partly different pathogenic mechanisms underlying septic- and traumatic-induced adult respiratory distress syndrome.

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.

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.

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.

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)

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.

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 cmH 2 O)). 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 (Q t ) and O 2 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, Q t and O 2 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. Q t and Os 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.

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.

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.

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.

To determine whether biologically active products of eosinophils, neutrophils and complement contribute to the development of adult respiratory distress system (ARDS) we measured eosinophil cationic protein (ECP), lactoferrin (LF) and C3a in bronchoalveolar lavage (BAL) and blood by means of radioimmunoassays. Seventeen patients served as controls. Fifteen patients were studied before and after major surgery to evaluate the influence of the surgical procedure, and 12 patients with ARDS were investigated 4–12 h after the onset of the disease.

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.