Treatment of thrombotic thrombocytopenic purpura with plasma exchange,antiplatelet agents,corticosteroid, and plasma infusion: Mayo clinic experience

Ten patients with thrombocytopenia (TTP) were treated recently in our institution with plasma exchange (PE), steroids, and antiplatelet drugs. Additionally, fresh frozen plasma (FFP) was administered to nine patients, with folic acid given to eight patients. After 13 to 25 months of follow-up, we found that four patients achieved and remained in remission after initial treatment. Three patients had four relapses, which developed while they were taking antiplatelet therapy, and which were treated successfully with FFP alone, or with PE in addition to FFP. Four patients suffered major neurological or renal damage during their presentation or initial treatment. One of these patients died during his initial hospitalization. Another patient died 7 months after initial treatment. After analyzing this experience, we have concluded that antiplatelet drugs or corticosteroid should be used as the sole initial treatment most cautiously. The relative importance of the exchange process, per se, versus plasma infusion cannot be inferred from our observations, but plasma exchange with FFP appears to have had a real impact on recovery.     

Economic evaluation of pooled solvent/detergent treated plasma versus single donor fresh-frozen plasma in patients receiving plasma transfusions in the United States

This study assessed the cost-effectiveness of Octaplas? versus fresh frozen plasma (FFP) in patients receiving plasma transfusions in the United States (US). Acute and long-term complications of plasma transfusions were modelled in a decision tree followed by a Markov model, using a healthcare payer perspective. Over a lifetime time horizon, patients receiving Octaplas? accumulate slightly more life years (0.00613 [95% uncertainty interval (95%UI): 0.00166–0.01561]) and quality-adjusted life years (QALY) (0.023 [95%UI: 0.012–0.044]) at lower cost compared with those treated with FFP. Octaplas? demonstrated to be the dominant treatment option over FFP (95%UI: Dominant–US$ 15,764/QALY).     

Anaphylatoxins in fresh-frozen plasma

BACKGROUND: Fresh-frozen plasma (FFP) is widely used in patients with coagulation disorders and simultaneous complement activation. Complement activation in FFP itself is poorly investigated. STUDY DESIGN AND METHODS: The concentration of anaphylatoxins C3a and C5a, the complement precursors C1q and factor B, and complement function were measured in 40 consecutively administered FFP units in two pediatric neonatal intensive care units. In 12 samples, the measurements were also performed after incubation with inulin. RESULTS: In 15 of 40 FFP units, both anaphylatoxin concentrations were below the upper cutoff levels reported for healthy humans (C3a, 500 microg/L; C5a, 5 microg/L). Anaphylatoxin levels were higher in FFP units produced by apheresis than in those from blood donation. Complement activation of FFP by inulin increased anaphylatoxin concentration, whereas C1q and factor B levels, and complement function remained unchanged. CONCLUSION: Elevated concentrations of anaphylatoxin are frequently found in FFP units produced by apheresis. Studies are necessary to investigate the reasons for complement activation and the possibilities of prevention during apheresis. As the concentrations of complement precursors and complement function did not change with activation in FFP, these studies should include measurement of the anaphylatoxins C3a and C5a.     

Stability of solvent/detergent-treated plasma and single-donor fresh-frozen plasma during 48 h after thawing.

The aim of this study was to compare the quality of solvent/detergent (SD) treated plasma, Octaplas, and single-donor fresh-frozen plasma (FFP) units during 48-h storage after thawing. Octaplas bags of different blood groups and individual FFP units were thawed and stored at either +4 degrees C or at room temperature (RT) for 48 h. Samples drawn during the observation period were investigated on various coagulation factor and protease inhibitor activities using standard coagulation and chromogenic assays. The generation of FVIIa was followed as a marker of coagulation factor activation. All investigated coagulation factors and protease inhibitors were stable for at least 8h during storage of Octaplas at +4 degrees C. FVIII levels started to decline earlier in FFP than in Octaplas at both storage temperatures. Stored Octaplas OD660 values were more stable during the storage period than FFP OD660 values, whereas VWF multimeric patterns were comparably stable in both types of plasma. In conclusion, this stability study has demonstrated that thawed Octaplas maintains its high quality, even with a time safety margin, for 8 h at +4 degrees C and for 6 h at RT. In general, there was more variability in coagulation factor levels among different FFP units compared with different Octaplas batches.     

The response of plasma fibronectin to acute myocardial infarction in humans

The purpose of this study was to investigate the plasma fibronectin response to complicated and uncomplicated acute myocardial infarction. All patients admitted to a Coronary Care Unit over a six-month period were prospectively assessed by measuring admission and daily plasma fibronectin levels using an electroimmunoassay. Of 166 patients admitted to the Unit, 66 were diagnosed as having an acute myocardial infarction. Plasma fibronectin levels were significantly lower 48 h after the onset of symptoms in 15 patients with a complicated acute myocardial infarction, compared to fibronectin levels in patients with an uncomplicated course; patients who had received intracoronary streptokinase had consistently higher plasma fibronectin levels than those seen in patients who did not receive this thrombolytic agent. This hepatocyte-derived plasma protein not only has diagnostic potential, but alterations in its levels may also provide insight into the systemic response to acute myocardial injury.     

Influence of epidural blockade on postoperative plasma fibronectin concentrations

To investigate the influence of neurogenic and hormonal stimuli during and after surgery on plasma fibronectin levels, 16 females undergoing cholecystectomy were studied. Eight patients received general anaesthesia, and eight also received a thoracic epidural block with local anaesthetic, which was maintained for 24 h postoperatively. The epidural group had significantly lower plasma levels of adrenaline and cortisol than the general anaesthesia group in the postoperative period. The previously well-documented early decrease in plasma fibronectin concentration following surgery was observed, and was essentially parallel with that of albumin, pre-albumin and thyroid hormones, with no differences between the groups. However, the restoration of the fibronectin level was slower in the epidural group, with significantly lower values as compared with controls at 48 and 72 h after surgery (p less than 0.01-0.001). It was concluded that the post-traumatic plasma fibronectin decrease is not mediated by neurogenic or adrenal stimuli. Such stimuli may, however, influence the subsequent restoration of the plasma fibronectin concentration.     

Cost-effectiveness and budget impact study of solvent/detergent (SD) treated plasma (octaplasLG®) versus fresh-frozen plasma (FFP) in any patient receiving transfusion in Canada

The objectives of this study were to evaluate the cost-effectiveness and budget impact of octaplasLG^® compared with fresh-frozen plasma (FFP) in all patients receiving a transfusion in Canada. A decision analytic framework was used to model acute and long-term complications that could follow plasma transfusion. Over a life time horizon, the cost with octaplasLG^® were CA$612.91, which is CA$303.14 less than those with FFP. OctaplasLG^® resulted in 0.021 quality adjusted life years (QALYs) gained in comparison with FFP. Because of higher efficacy and lower costs, octaplasLG^® is expected to be the dominant treatment option over FFP in Canada.     

A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation

BACKGROUND: Virus inactivation of pooled fresh-frozen plasma (FFP) by the solvent/detergent (SD) method results in a loss of approximately 20 percent of factor VIII. This study aimed to assess the efficacy of SD-treated plasma in correcting the coagulopathy associated with liver disease and liver transplantation. STUDY DESIGN AND METHODS: Forty-nine patients with coagulation deficits due to liver disease, who required FFP for invasive procedures or liver transplantation, were randomly assigned to receive either FFP or SD-treated plasma. Patients were assessed for side effects, correction of coagulopathy over 24 hours, and seroconversion for viral markers 6 to 18 months after treatment. RESULTS: In the liver disease group, equal correction of clotting factors and partial thromboplastin time was seen with FFP and SD-treated plasma, with a similar return to baseline values over 24 hours. There was greater correction of the International Normalised Ratio in patients receiving SD-treated plasma (p = 0.037), but this patient group had higher baseline values than recipients of FFP (p = 0.024). Liver transplant patients also showed equivalent correction of coagulopathy with the same dose of FFP and SD-treated plasma. The use of other blood components during transplantation was identical in the two treatment groups. No seroconversions were seen for HIV or hepatitis B or C virus. One patient who had received FFP seroconverted for human parvovirus B19. Apparent seroconversion for hepatitis A virus seen at 9 to 13 months in four other patients was probably due to detection of passively transferred antibodies, as later testing of these patients gave negative results. Minor side effects were rare in both groups. CONCLUSION: SD-treated plasma is an efficacious source of coagulation factors for patients with liver disease who are undergoing biopsy or transplantation. Assessment of seroconversion for viral markers in recipients of plasma-derived products and plasma components should include consideration of the possibility that passively transferred antibodies were detected.     

Coagulation parameters of CPD fresh-frozen plasma and CPD cryoprecipitate-poor plasma after storage at 4 degrees C for 28 days

A pilot study was performed on the storage of plasma and cryosupernatant plasma at 4 degrees C for up to 28 days. Eight bags, four of CPD fresh-frozen plasma (FFP) and four of CPD cryosupernatant plasma (CSP, plasma without cryoprecipitate), were sampled during storage for assays of pH; factors V, VIII, IX, and XI; fibrinogen; prothrombin time; activated partial thromboplastin time (APTT); plasma protein electrophoresis; viscosity; and C1q binding. No changes were found in viscosity or the plasma protein electrophoretic pattern, and there was no detectable immune complex formation. The fibrinogen concentration remained constant, and the prothrombin time showed a gradual increase of 2.5 seconds for both groups of plasma. The labile coagulation factor V decreased gradually for FFP and CSP to 58 and 64 percent of its initial value, respectively (51 +/− 8% and 54 +/− 6% of the value of fresh pooled plasma). Factor VIII decreased to 36 percent of its initial value in FFP (48 +/− 14% of fresh pooled plasma). In CSP, factor VIII decreased after 28 days to 7 percent of its initial value (7 +/− 1% of fresh pooled plasma). The APTT increased for FFP from 28 to 35.8 +/− 1.1 seconds and for CSP from 36 to 49.5 +/− 4.9 seconds. The only chemical change observed for both plasmas was a rise in pH, from 7.27 to 7.56, after 28 days. The results of this pilot study indicate that FFP can be stored at 4 degrees C for 28 days with sufficient recovery of coagulation factors to maintain hemostasis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cascade filtration for TTP: an effective alternative to plasma exchange with cryodepleted plasma

TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.     

Measurement of plasma fibronectin in patients who develop the adult respiratory distress syndrome

Depletion of plasma fibronectin has been observed in certain clinical conditions predisposing to the adult respiratory distress syndrome and has been associated with cardiopulmonary dysfunction in experimental lung injury. We evaluated prospectively the relationship between plasma fibronectin concentration and the development of the adult respiratory distress syndrome in patients known to be at high risk. Although plasma fibronectin levels in participants at study entry were lower in this population (mean 258 +/- 132 micrograms/ml) than in normal volunteers (461 +/- 127 micrograms/ml, p less than 0.0025), there was no difference between patients who subsequently developed the adult distress syndrome (mean 255 +/- 149 micrograms/ml) and those with similar illness or injury who did not develop the syndrome (260 +/- 126 micrograms/ml). Fibronectin concentration was not further depressed even after development of adult respiratory distress syndrome and did not correlate with degree of pulmonary dysfunction. These data suggest that fibronectin depletion is not an important determinant of respiratory failure in humans. Patients with sepsis syndrome had significantly lower plasma fibronectin levels than those without sepsis (187 +/- 119 micrograms/ml vs. 273 +/- 131 micrograms/ml, p less than 0.05), suggesting a possible role for fibronectin in the pathogenesis of sepsis.     

Influence of epidural blockade on postoperative plasma fibronectin concentrations

To investigate the influence of neurogenic and hormonal stimuli during and after surgery on plasma fibronectin levels, 16 females undergoing cholecystectomy were studied. Eight patients received general anaesthesia, and eight also received a thoracic epidural block with local anaesthetic, which was maintained for 24 h postoperatively. The epidural group had significantly lower plasma levels of adrenaline and Cortisol than the general anaesthesia group in the postoperative period. The previously well-documented early decrease in plasma fibronectin concentration following surgery was observed, and was essentially parallel with that of albumin, pre-albumin and thyroid hormones, with no differences between the groups. However, the restoration of the fibronectin level was slower in the epidural group, with significantly lower values as compared with controls at 48 and 72 h after surgery (p<0.01–0.001). It was concluded that the post-traumatic plasma fibronectin decrease is not mediated by neurogenic or adrenal stimuli. Such stimuli may, however, influence the subsequent restoration of the plasma fibronectin concentration.     

White cells in fresh-frozen plasma: evaluation of a new white cell- reduction filter

BACKGROUND: Fresh-frozen plasma (FFP) has generally been regarded as an acellular component. Recently, viable lymphocytes have been detected in this component and the question of irradiation of FFP for certain patients has been raised. Whether the numbers of white cells (WBCs) in FFP are sufficient to require WBC-reduction of acellular components for patients receiving WBC-reduced cellular components has not been determined. WBC numbers in FFP were examined, and the performance of a new commercial WBC-reduction filter for FFP was assessed. STUDY DESIGN AND METHODS: WBC numbers in plasma processed for use as FFP and in thawed FFP were counted before and after WBC-reduction filtration by the use of flow cytometry Fast and slow filtration was used to simulate laboratory and bedside filtration, respectively. Three different methods for plasma harvesting (soft-spin, hard-spin, and second-spin methods) were assessed. The filter capacity was also examined. RESULTS: The numbers of WBCs in plasma covered a three-log10 range (soft-spin method, 0.04-3.6 × 10(6); hard-spin method, 0.47-45.4 × 10(6); second- spin method, 0.4–37.2 × 10(6)). For the hard-spin and second-spin methods which produced the greatest plasma yields, 92 percent and 85.7 percent of bags, respectively, had counts>1 × 10(6) and 43 percent (hard-spin method) and 45.7 percent (second-spin method) had counts>5 × 10(6). There was no significant difference between the counts obtained in plasma and thawed FFP. The filter reduced WBC numbers to <1 × 10(5) in all but 3 of 49 bags. In the remaining three, there were <2 × 10(5) WBCs. Five bags of plasma could be processed effectively through each filter. CONCLUSION: FFP may contain WBC numbers above the threshold at which the use of WBC-reduction filters for cellular components in some patients is necessary. Confirmation of these findings and similar investigations on plasma prepared by other methods may help in defining a role for the use of WBC-reduction filters for FFP     

严重烧伤休克期心脏调节肽变化的研究

目的探讨严重烧伤休克期血浆降钙素基因相关肽(CGRP)和神经肽Y(NPY)变化及其意义。方法采用放射免疫法(RA)测定60例严重烧伤患者休克期不同时相点血浆CGRP、NPY含量。结果严重烧伤休克期后3 h血浆CGRP降低,12 h达最低值,伤后48 h仍低于正常对照组(P<0.05);血浆NPY于伤后1 h升高,12 h达峰值,48 h仍高于正常对照组(P<0.05),血浆CGRP与NPY呈显著负相关(P<0.01)。结论血浆CGRP降低、NPY升高在严重烧伤休克期中起着重要作用,可能参与和促进了烧伤休克发生和发展。     

Coagulation parameters in apheresis and leukodepleted whole-blood plasma during storage

BACKGROUND: Thawing fresh-frozen plasma (FFP) may cause delay in delivery, and one approach to circumvent this is to store plasma at +4 degrees C. Thawed plasma is commonly discarded after a few days of storage, owing to the assumption that coagulation factor activity decreases to clinically unacceptable levels. STUDY DESIGN AND METHODS: Eighteen apheresis plasma (AP) units were collected from blood donors. The collected plasma was divided into two equal parts: one part frozen at -74 degrees C as FFP and one part stored at +4 degrees C as fresh liquid plasma (FLP). Thirty-nine units of whole blood (WB) were collected from blood donors and leukodepleted by inline filtration, followed by plasma separation. Twenty plasma units were frozen at -74 degrees C as FFP and 19 plasma units were stored at +4 degrees C as FLP for 28 days. Plasma aliquots were collected before freezing and immediately after thawing FFP and before and during storage of FLP at Days 14 and 28. Factor (F)V, FVIII, D-dimers, and C1-esterase inhibitor levels were assessed. RESULTS: No significant differences in coagulation factor levels were assessed between FLP prepared from AP and FLP prepared from WB. FV and FVIII levels decreased on average 25 and 50 percent, respectively, at Day 14 of storage. C1-esterase inhibitor and D-dimers levels were not affected. CONCLUSION: Leukodepleted apheresis and WB plasma stored for 14 days retain sufficient levels of FV and FVIII activity for maintenance of normal hemostasis and could therefore be considered useful in selected clinical situations.     

Elevated plasma levels of ED1+ ("cellular") fibronectin in patients with vascular injury

Using an enzyme-linked immunosorbent assay, we measured the concentration of fibronectin containing an extra type III domain (ED1) in the circulation of humans. Plasma levels of ED1 + fibronectin averaged 2.8 +/- 1.0 micrograms/ml in healthy individuals and did not differ substantially according to age or sex. In comparison with those from normal subjects, plasma samples obtained from patients with collagen vascular disorders contained increased average levels of ED1 + fibronectin. Among this group, levels of ED1 + fibronectin were significantly greater in samples taken from individuals with clinical evidence of vasculitis. Although levels of total (ED1 + plus ED1 -) fibronectin were also elevated in plasma samples from patients with vasculitis, only the concentration of the ED1 + variant correlated with severity of disease in two patients examined serially. Elevations in plasma content of ED1 + fibronectin, but not total fibronectin, were also noted in patients with acute vascular tissue injury associated with major trauma or sepsis syndrome. Western blot examination revealed the presence of intact dimeric ED1 + fibronectin in the circulation of all patients studied, although fragments bearing the ED1 were also detected. Human plasma normally contains small quantities of soluble ED1 + ("cellular") fibronectin, and these levels are increased in disorders involving vascular injury.     

Modification of fresh-frozen plasma transfusion practices through educational intervention

The effect of an educational program designed to address misconceptions about the perioperative transfusion of fresh-frozen plasma (FFP) was examined. Results of a baseline audit of FFP use were compared to those of a study subsequent to the educational process. Statistical analysis of the data revealed that the decrease in the number of patients transfused with FFP, from 32 of 2077 operative cases in Group A (baseline) to 18 of 2540 operative cases in Group B (after education), was significant (p less than 0.01). Analysis of the justifications given for transfusion of FFP revealed that the increase in acceptable indications from 47 percent in Group A to 78 percent in Group B was also significant (p less than 0.05). There was no significant difference between the two groups in units of FFP transfused per patient (Group A, 3.66 +/- 3.2, vs. Group B, 2.47 +/- 1.7) or red cells (Group A, 2.84 +/- 5.2, vs. Group B, 5.22 +/- 4.4), and the patterns of platelet transfusion were similar in the two groups. There was a significant difference in the postoperative partial thromboplastin time (Group A, 38.2 +/- 8.7 vs. Group B, 56.3 +/- 24 seconds, p less than 0.01) but no significant difference in postoperative prothrombin time (Group A, 14.1 +/- 2.6 vs. Group B, 15.4 +/- 3.3 seconds). It can be concluded that an educational program designed to address misconceptions in transfusion practice can alter physician performance and thereby reduce the inappropriate use of FFP.     

Decrease of plasma fibronectin concentration following infusion of a gelatin-based plasma substitute in man

Intravenous infusion of 500 ml of a gelatin-based plasma substitute, Haemaccel, given to healthy volunteers, resulted in a significant decrease of the immunoreactive plasma fibronectin concentration 48 h and 72 h after infusion. One hour after infusion, the ability of fibronectin to bind gelatin was inhibited with a gradual recovery within 48 h. A dextran based plasma substitute, Macrodex, did not have this effect on plasma fibronectin.     

REVIEWS: Hemostatic resuscitation for massive bleeding: the paradigm of plasma and platelets—a review of the current literature

BACKGROUND: Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists. Recent studies indicate a possible survival benefit in patients receiving a higher ratio of plasma and platelets (PLTs) to red blood cells (RBCs) than what is recommended in current transfusion guidelines. STUDY DESIGN AND METHODS: English databases were searched for reports of patients receiving massive transfusion that tested the effects of administration of plasma and/or PLTs in relation to RBCs on survival from January 1990 to March 2009. RESULTS: Fourteen retrospective studies involving 4594 patients were identified. Six tested the effect on survival in relation to fresh‐frozen plasma (FFP)‐to‐RBC ratio, and five investigated FFP‐ and PLT‐to‐RBC ratios. Two studies evaluated implementation of massive transfusion protocols with preemptive FFP and PLT administration; one study based transfusion therapy on the result of the thrombelastograph (TEG) analysis versus historic controls. All studies reviewed demonstrate a survival benefit for patients who receive more FFP and PLT as part of the hemostatic resuscitation. When TEG was used to guide transfusion therapy an increase in FFP and PLT was also seen when compared to historic controls and this was associated with improved survival. CONCLUSIONS: High FFP‐ and PLT‐to‐RBC ratios seem to improve survival in patients with massive bleeding. Randomized studies evaluating TEG‐guided transfusion therapy versus fixed ratios of plasma and PLTs to RBCs in massively bleeding patients is highly warranted.     

Effects of circulating endogenous catecholamines on plasma glucose, potassium and magnesium

1. To examine the metabolic effects of increases in circulating endogenous plasma catecholamines, we measured plasma glucose, potassium and magnesium in 14 patients undergoing elective coronary artery bypass grafting. The patients were randomized into two groups and received either sodium nitroprusside (a direct-acting vasodilator) or trimetaphan camsylate (a ganglion-blocking agent) for routine control of blood pressure during the operation. 2. There were significant differences between the two groups in the levels of all three metabolic variables studied. Plasma glucose levels rose in both groups, but were significantly higher in the sodium nitroprusside group [peak levels 9.14 (SEM 0.72)mmol/l compared with 6.71 (0.88) mmol/l, P less than 0.001, analysis of variance]. The cardioplegia solution caused a large increase in plasma magnesium in both groups but in the sodium nitroprusside group the level rose higher [to 1.59 (0.12)mmol/l compared with 1.34 (0.06)mmol/l] and fell faster (P less than 0.05, analysis of variance). In the group receiving sodium nitroprusside, plasma potassium fell, by a mean of 0.34mmol/l, as plasma catecholamine levels rose; no such fall was seen in the group receiving trimetaphan camsylate (P less than 0.05, analysis of variance). 3. It is concluded that the sympathoadrenal system is important in causing metabolic changes during cardiopulmonary bypass and may be relevant in other conditions such as acute myocardial infarction.