Beta-blocking agents during electroconvulsive therapy: a review.

Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary.

Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma.

BACKGROUND: Surgery on pheochromocytoma carries a risk for hemodynamic (HD) instability. The aim of this study was to identify preoperative risk factors for intraoperative HD instability. In addition, efficacy of pretreatment with the alpha-adrenergic receptor (alpha) antagonists phenoxybenzamine (PXB) and doxazosin (DOX) was compared with respect to reduction of intraoperative HD instability. METHODS: Seventy-three patients operated in Erasmus Medical Center between 1995 and 2007 were included. Parameters studied were catecholamine type and concentration, tumor diameter, mean arterial pressure (MAP) before and after (MAP(alpha)) pretreatment with alpha-antagonist, postural fall in blood pressure (BP) after pretreatment, type of alpha-blockade, type of operation, and presence of a familial polytumor syndrome. HD instability was assessed by measuring the number and time period MAP was below 60 mm Hg and systolic BP (SBP) was above 160 mm Hg. RESULTS: A correlation was found between the intraoperative time periods of SBP above 160 mm Hg and plasma norepinephrine levels (r = 0.23; P < 0.05), tumor diameter (r = 0.36; P < 0.01), and postural BP fall (r = 0.30; P < 0.05). MAP at presentation and after alpha-blockade above 100 mm Hg (BP, 130/85 mm Hg) was related to more and longer episodes with a SBP above 160 mm Hg (P < 0.01). Type of operation or alpha-blockade and presence of a familial polytumor syndrome were not related to intraoperative HD instability. Postoperative MAP was lower in the DOX group than in the PXB group (P < 0.05). CONCLUSION: Risk factors for HD instability during surgery for pheochromocytoma include a high plasma NE concentration, larger tumor size, more profound postural BP fall after alpha-blockade, and a MAP above 100 mm Hg (130/85 mm Hg). Efficacy for preventing HD instability was identical for PXB and DOX.

[Liver transplantation with a living donor: the first 3 cases in Rotterdam]. / Levertransplantatie met een levende donor: de eerste 3 casussen in Rotterdam.

Liver transplantation with a part of the liver from a healthy living donor can be life saving for selected patients with end-stage liver failure. The experiences with the first 3 adult patients in the Netherlands were as follows. The first patient was a 56-year-old man with primary sclerosing cholangitis, who received half of the liver from his 53-year-old sister. Postoperatively, the donor developed a urinary tract infection, which was treated with antibiotics. The recipient developed fever and paralytic ileus 6 days after transplantation. Relaparotomy revealed minimal bile leakage from the cut surface of the liver, which was corrected with a suture. Three years after donation, both donor and recipient were doing well. The second patient was a 63-year-old man with hepatic cirrhosis due to hepatitis B, recurrent bleeding from varices, and hepatocellular carcinoma. The carcinoma was treated percutaneously with radiofrequency ablation. He was given a liver transplant from his 28-year-old son. The donor later developed transient ileus and mild liver function disorders. The recipient developed a bacterial infection of the ascites, which was treated with antibiotics, and later Candida-oesophagitis and a herpes simplex infection, which were also treated successfully. More than 2 years after donation and transplantation, both donor and recipient were in good condition. The third patient was a 42-year-old man with a chronic hepatitis B virus infection and 2 hepatocellular carcinomas. The donor was his 34-year-old sister-in-law. The recipient developed prolonged jaundice due to stenosis at the site of the bile duct anastomosis, for which a stent was placed. He was discharged in good condition but died 11 months later of cerebral metastases. One year after the procedure, the donor was doing well. The Rotterdam liver transplantation programme with living donors demonstrates that excellent results can be accomplished with minimal risk for the donor.

[Beta-blockers and electroconvulsive therapy: a review]. / Prevention of post-discharge suicide: an inventory.

BACKGROUND: When patients with cardiovascular disorders undergo electroconvulsive therapy (ect) they sometimes have to be treated for tachycardia and high blood pressure. AIM: To describe the effects of beta-blockers on seizure duration and cardiovascular variables in patients undergoing ect. METHOD: Search for studies in Medline, with the keywords 'beta-adrenergic blocking agents' and 'electroconvulsive therapy'. Only articles based on randomised placebo-controlled investigations were included. results The search strategy produced 21 articles. These were assessed by all authors. Esmolol was the drug administered in most of the trials. Since seizure duration can influence the therapeutic effect of ect it is advisable to use bilateral electrode placement in patients with cardiovascular risk factors and to administer esmolol prior to seizure induction. CONCLUSION: The beta-blocker of choice for use during ect seems to be esmolol; it can shorten seizure duration, although the effect is probably dose-dependent. Esmolol is also the drug of choice in ect sessions for patients without cardiovascular risk factors but who develop prolonged hypertension or tachycardia. A possible alternative is labetalol, but its longer half-life is a disadvantage, particularly if it is administered in a high dose. So far, experience with landiolol is limited, but its short half-life, greater cardioselectivity and higher potency mean that it could be a promising alternative.

Perioperative pharmacokinetics of cefotaxime in serum and bile during continuous and intermittent infusion in liver transplant patients.

BACKGROUND: Drug pharmacokinetics may be altered during liver transplantation. Cefotaxime (CTX), used as perioperative prophylaxis, demonstrates time-dependent killing and therefore continuous infusion might have pharmacodynamic advantages. OBJECTIVES: To determine the pharmacokinetics of CTX and desacetylcefotaxime (DCTX) in serum, bile and urine during continuous and intermittent infusion when performing liver transplantation. METHODS: Fifteen patients undergoing liver transplantation were studied after continuous infusion (CI) (4000 mg iv per 24 h following a loading dose of 1000 mg) and intermittent bolus infusion (BI) (1000 mg iv four times daily). Samples were collected during the first 48 h after liver transplantation. Concentrations of CTX and DCTX were determined by HPLC. RESULTS: During surgery, the mean concentration in serum after CI was 18 mg/L. The lowest serum concentration was 5 mg/L in the CI group and levels were undetectable in the BI group. Target serum concentrations of > or =4 mg/L were reached for 100% of the dosing interval during CI and approximately 60% during BI. Post-operatively, the mean concentration in serum after CI was 26 mg/L. The lowest serum concentration was 8 mg/L in the CI group and levels were undetectable after BI. The peroperative pharmacokinetics of CTX in this patient group were deranged and variable, mainly caused by an increased volume of distribution and decreased hepatic clearance. Metabolism was hampered, but DCTX area under the curve (AUC)/CTX AUC ratios varying between 0.7-0.9 were reached peroperatively. Post-operatively, DCTX AUC/CTX AUC ratios were higher (1.1-1.4). Unchanged CTX in bile was approximately 0.1% of the administered dose, leading to concentrations >4 mg/L throughout the dosing interval for both regimens. CONCLUSION: Although an intermittent bolus infusion of CTX 1000 mg produces t > target concentration for 60% of the dosing interval during liver transplantation, serum concentrations may be insufficient during the reperfusion phase. Continuous infusion overcomes this. Post-operatively, CTX clearance is impaired by decreased metabolic clearance and there is substantial accumulation of DCTX. In bile, sufficient concentrations of CTX and its active metabolite are reached with both regimens.

Aprotinin in orthotopic liver transplantation: evidence for a prohemostatic, but not a prothrombotic, effect.

Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation (fibrinogen level, activated partial thromboplastin time [aPTT], prothrombin time, and platelet count) and fibrinolytic variables (tissue-type plasminogen activator [tPA] antigen and activity, plasminogen activator inhibitor activity, and D-dimer), as well as thromboelastography (reaction time [r], clot formation time, and maximum amplitude) in 27 patients administered either high-dose aprotinin (2 x 10(6) kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 x 10(6) KIU/h, and 1 x 10(6) KIU before reperfusion; n = 10), regular-dose aprotinin (2 x 10(6) KIU at induction and continuous infusion of 0.5 x 10(6) KIU/h; n = 8), or placebo (n = 9) during OLT. Blood samples were drawn at seven standardized intraoperative times. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dimer and tPA antigen levels) was significantly lower in aprotinin-treated patients compared with the placebo group. Interestingly, coagulation times (aPTT and r) were significantly more prolonged in aprotinin-treated patients than the placebo group. No difference was seen in the incidence of perioperative thrombotic complications in the entire study population (n = 137). Aprotinin has an anticoagulant rather than a procoagulant effect. Its blood-sparing (prohemostatic) effect appears to be the overall result of a strong antifibrinolytic and a weaker anticoagulant effect. These findings argue against a prothrombotic effect of aprotinin in patients undergoing OLT.

Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group.

BACKGROUND: Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements. METHODS: We did a randomised, double-blind, placebo-controlled trial in which six liver-transplant centres participated. Patients undergoing primary liver transplantation were randomly assigned intraoperative high-dose aprotinin, regular-dose aprotinin, or placebo. Primary endpoints were intraoperative blood loss and transfusion requirements. Secondary endpoints were perioperative fluid requirements, postoperative blood transfusions, complications, and mortality. FINDINGS: 137 patients received high-dose aprotinin (n=46), regular-dose aprotinin (n=43), or placebo (n=48). Intraoperative blood loss was significantly lower in the aprotinin-treated patients, with a reduction of 60% in the high-dose group and 44% in the regular-dose group, compared with the placebo group (p=0.03). Total amount of red blood cell (homologous and autologous) transfusion requirements was 37% lower in the high-dose group and 20% lower in the regular-dose group, than in the placebo group (p=0.02). Thromboembolic events occurred in two patients in the high-dose group, none in the regular-dose group, and in two patients in the placebo group (p=0.39). Mortality at 30 days did not differ between the three groups (6.5%, 4.7%, and 8.3%; p=0.79). INTERPRETATION: Intraoperative use of aprotinin in adult patients undergoing orthotopic liver transplantation significantly reduces blood-transfusion requirements and should be routinely used in patients without contraindications.

The effects of long-term graft preservation and prostaglandin E1 on intraoperative hemodynamic changes in liver transplantation. A comparison between orthotopic and heterotopic transplantation in the pig.

The study aimed to compare the intraoperative hemodynamic changes during orthotopic liver transplantation (OLT) with those during heterotopic liver transplantation (HLT) after different durations of cold storage of the graft. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Sixty-nine female Yorkshire pigs underwent either OLT (n = 32) or HLT (n = 37) with a graft stored for 2 hr (n = 31), 24 hr (n = 16), 48 hr (n = 7), or 72 hr (n = 15). In 16 transplantations in the various groups, PGE1 was given intravenously to both donor and recipient animals and it was added to the preservation and flushing solutions. Univariate nonparametric tests (Mann-Whitney and Wilcoxon rank-sum) were used for analysis of cardiac output (CO), mean arterial pressure (MAP), left and right ventricular minute work (LVMW, RVMW), pulmonary capillary wedge pressure (PCWP), and systemic and pulmonary vascular resistance (SVR, PVR), at different intervals during the operative procedure. For the three main variables--i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. During HLT, portal vein clamping lowered MAP and CO, while during the anhepatic phase in OLT, SVR increased and CO dropped. After recirculation of the graft, an increase in PVR and a decrease in SVR were found in both OLT and HLT. At different stages of the surgical procedure, longer graft storage time diminished CO and MAP (P less than 0.001), especially in OLT. PGE1 appeared to reduce the cardiovascular reserves needed to compensate the changes after recirculation of the graft. The observed differences in intraoperative hemodynamics between OLT and HLT can partly be attributed to differences in operative techniques. Extension of the graft preservation period resulted in poor cardiac performance, more so in OLT than HLT. The native liver in HLT might be able to metabolize the presumed myocardial depressant factors, released by the graft upon reperfusion. Prostaglandin E1 did not protect against the reperfusion syndrome.

Pharmacokinetics of low-molecular-weight heparin and unfractionated heparin during elective aortobifemoral bypass grafting.

Perioperative monitoring has demonstrated that administration of heparin on an empirical basis is associated with a wide variation in patient response and elimination rate. This problem may be overcome by intervention on the basis of perioperative monitoring or by using forms of heparin with different pharmacokinetic properties. When compared with unfractionated heparin, low-molecular-weight heparin has a higher bioavailability after subcutaneous administration, a linear clearance mechanism with a prolonged half-life, and is at least as effective in preventing postoperative vein thrombosis. Theoretically these characteristics of low-molecular-weight heparin could lead to more predictable levels of heparin activity. In this study we compared the pharmacokinetics of low-molecular-weight heparin and unfractionated heparin after an intravenous injection in patients undergoing aortic graft surgery. Heparin activity was measured before heparin administration and at 5, 20, 35, 50, 65, 80, 95, and 110 minutes after administration. The anti-Xa activity in the low-molecular-weight heparin group showed less variation and was more sustained when compared to the unfractionated heparin group. Fibrin degradation products were moderately correlated with the anti-factor Xa levels of the low-molecular-weight heparin group, but no correlation was found in the unfractionated heparin group. The anti-factor Xa activity of low-molecular-weight heparin was, in contrast to that of unfractionated heparin, not completely reversible by protamine administration. The blood loss was comparable in both groups. In contrast to what was expected, the pharmacokinetic profiles of low-molecular-weight heparin and unfractionated heparin showed a similarity after intravenous injection in patients undergoing aortobifemoral bypass grafting. Factors that could have influenced the pharmacokinetic behavior of heparin are discussed.

A comparative study on changes in hemostasis in orthotopic and auxiliary liver transplantation in pigs.

We compared blood loss and hemostasis in pigs which had undergone either orthotopic liver transplantation (OLT) (group A, n = 12) or auxiliary heterotopic partial liver transplantation (APLT) (group B, n = 11). Blood samples were taken at regular intervals during and after the operations. In both groups, nine animals survived longer than 24 h and data from these animals were used for analysis. Median (range) intraoperative blood loss was 825 ml (250-1500 ml) in OLT and 425 ml (300-750) in APLT (P less than 0.01). Routine clotting times, as the activated partial thromboplastin time, prothrombin time and thrombin time, showed no major intraoperative changes in either group. Fibrinogen levels decreased in both groups, but no significant difference was found between the two groups. The only significant difference between group A and B was a more sustained increase in fibrinolytic activity after graft recirculation in group A. Postoperatively, restoration of fibrinogen, antithrombin-III and alpha 2-antiplasmin levels was slightly faster in group B, resulting in significantly higher levels during the first day. We conclude that, in this animal model, APLT is associated with significantly lower blood loss and less severe fibrinolytic activity, than OLT. This difference might result from the lack of an anhepatic period and the reduced surgical trauma in auxiliary heterotopic liver transplantation.

[Possibilities and limitations of heterotopic auxiliary liver transplantation]. / Möglichkeiten und Grenzen der heterotopen auxiliären Lebertransplantation.

Although auxiliary heterotopic liver transplantation offers theoretical advantages over orthotopic liver replacement, clinical results have heretofore been dismal. After development of a technique of reduced size liver grafts provided with portal and arterial blood and venous drainage via the suprahepatic V. cava (HLT) in experimental animals, this method was applied in 21 transplantations in 19 patients. 11 of 16 patients with chronic liver insufficiency and one of three patients with fulminant liver failure survived transplantation for at least 1 year. HLT was well tolerated even by high-risk patients. Possibilities and limitations of this novel approach are discussed.

Intraoperative hemodynamics in liver transplantation comparing orthotopic with heterotopic transplantation in the pig.

The intraoperative hemodynamic changes and several graft function parameters were studied comparing orthotopic liver transplantation with auxiliary partial liver transplantation (APLT) in the pig. Thirty-one Yorkshire pigs (ca. 25 kg b.w.) were randomly allocated to OLT (n = 16) or APLT (n = 15). During the construction of portal anastomosis the median cardiac output dropped to 67% of the initial value in OLT and to 49% in APLT (P less than 0.02). Median duration of the portal flow interruption was shorter in APLT: 15 min versus 48 min in OLT (P less than 0.002). After unclamping of the aorta, the median systolic blood pressure dropped to 75 mmHg in OLT and to 90 mmHg in APLT (P less than 0.02). APLT is less time-consuming: median duration of transplantation was 128 min versus 165 min in OLT (P less than 0.002). SGOT levels were lower in APLT than in OLT (median SGOT on the first postoperative day 67 was IU/L versus 177 IU/L, P less than 0.002). It is concluded that APLT is a shorter procedure than OLT with a shorter portal flow interruption, being less offensive to the recipient.

Auxiliary partial liver transplantation for end-stage chronic liver disease.

Auxiliary heterotopic liver transplantation is theoretically attractive because it leaves the recipient's liver in place. The surgical trauma of hepatectomy is avoided, and failure of the graft does not necessarily lead to the death of the patient or a second, emergency transplantation. Another advantage is that matching the body sizes of the donor and the recipient is not mandatory, which increases the number of possible donors. However, previous clinical results of auxiliary liver transplantation have been poor. We performed auxiliary partial liver transplantation in six consecutive patients with end-stage chronic liver disease who were not accepted for orthotopic liver transplantation because they had massive ascites, deficient clotting function, cachexia, or poor pulmonary reserve. The donor liver was transplanted to the right subhepatic region after removal of segments II and III, and it was provided with portal and arterial blood. There were no major changes in hemodynamic measurements during surgery. The mean hospital stay after transplantation was 22.7 days (range, 14 to 29). After a mean follow-up period of 14 months (range, 5 to 23), all patients were alive, with good graft function as demonstrated by scintigraphy, Doppler ultrasonography, and synthesis of clotting factors. From these observations we conclude that auxiliary partial liver transplantation is an attractive alternative to orthotopic liver transplantation in high-risk patients. Its role in other patients who need liver transplants remains to be defined.

Monitoring heparin and haemostasis during reconstruction of the abdominal aorta.

In spite of its unpredictable kinetics, heparin is still not generally monitored during peripheral vascular surgery. To evaluate heparin levels and neutralisation, plasma heparin concentrations were measured using a chromogenic substate method during 20 consecutive operations on the Abdominal Aorta. This was combined with measuring activated partial thromboplastin time (APTT), thrombin time (ThT), prothrombin time (PT), antithrombin-III (AT-III) and fibrinogen concentration. Heparin concentration 5 min after administration and the elimination rate showed a wide variation. Using a standard dosage for all patients resulted in plasma heparin levels that are potentially too low in some patients. The APTT and ThT were found to be unsuitable for an exact calculation of heparin levels. Protamine administration based on the surgeon's judgement of haemostasis was inadequate. Furthermore an intraoperative decrease of AT-III and fibrinogen was seen in eight patients. It is advisable and possible to have direct monitoring of heparin concentration during peripheral vascular surgery.