Fatal Takotsubo cardiomyopathy due to epinephrine in shoulder arthroscopy.

The authors report a case of a shoulder arthroscopy in which epinephrine saline irrigation was held responsible for acute hypertension followed by fatal Takotsubo cardiomyopathy.

Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation.

BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the interaction of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the subendothelial matrix. We hypothesized that the use of organs from animals with homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD or control pig kidney xenografts. XNA levels, coagulation, and platelet activation markers were studied, and specimens of rejected kidneys were analyzed histologically. RESULTS: Although XNA depletion was comparable in both groups, neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine kidneys showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical analysis revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys, whereas it was undetectable in the nongrafted vWD kidneys, suggesting the deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of vWD organs did not improve the survival time of grafted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as complement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation process during xenograft rejection.

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Assessment of hyperacute rejection in a rat-to-primate cardiac xenograft model.

We studied a rat-to-cynomolgous monkey model for xenotransplantation of vascularized organs and found that a rat heart was rejected in 5.5 +/- 1.4 min (n = 10). This hyperacute rejection (HAR) was consistent with kinetic experiments in vitro that showed damage to rat endothelial cells (ECs) after 3 min of incubation with primate serum. Histopathology and ultrastructural analysis of rejected hearts showed marked EC damage and early adherence of platelets and polymorphonuclear leukocytes to the endothelium. Immunohistochemical analysis revealed deposition along endothelial surfaces of IgG, IgM, and complement (C) components of the classical but not the alternative pathway, suggesting that, as in the pig-to-primate model, HAR is mediated by the binding of recipient xenogeneic natural antibodies and C activation. The effect of C depletion on xenograft survival was evaluated in two recipients that were treated with cobra venom factor (CVF). CVF caused complete C inactivation, demonstrated by lack of serum hemolytic activity and C-dependent EC cytotoxicity at engraftment and until the animals died. The rat cardiac transplants survived for at least 9 hr and 77 hr. Histology showed massive interstitial hemorrhage, edema, and cellular infiltration with scanty fibrin deposits. These results in CVF-treated recipient monkeys indicate that C activation mediates the development of HAR in this rat-to-primate model. We suggest that the model may be of interest as an alternative to the more expensive and time-consuming pig-to-primate model for testing the efficacy of transgenic modification of donor organs to prolong xenograft survival and for studying mechanisms of discordant xenograft rejection.

Liver grafts can be preserved overnight.

The introduction of University of Wisconsin solution has made liver transplantation a semi-elective procedure. However, many studies have suggested that cold storage must not exceed 12 hours to avoid ischemic-type biliary complications, to reduce the incidence of primary nonfunction and to improve graft and patient survival. The aim of this study was to compare the function of livers transplanted as soon as possible after the liver was harvested and those preserved overnight. Over a 42-month period, we studied 133 elective orthotopic liver transplantation procedures. When cold ischemia started after 6 PM, patients underwent transplantation the following morning (group A), whereas the remainder underwent transplantation immediately (group B). Cold ischemia lasted 13.7 hours and 9.5 hours in groups A and B, respectively (P < .001). The two groups were comparable in terms of initial and late biochemical liver function, the rates of primary nonfunction (6.5% in group A, 6.8% in group B), acute rejection (45.6% in group A, 45.7% in group B), and vascular and infectious complications. No ischemic-type biliary complications were observed. Graft and patient survival were similar in both groups (72.4% v 75.4% and 72.9% v 75.8% in groups A and B, respectively). These results suggest that having taken a cut off at 6 PM to divide the groups into those that underwent transplantation consecutively and those deferred to the morning, the difference between the two groups in terms of storage is relatively modest. Elective liver transplantation can be performed after overnight graft storage without increasing short-term or long-term morbidity or mortality rates.

[Evaluation of a new technique of extracorporeal perfusion of the swine liver on a swine-primate model]. / Evaluation d'une nouvelle technique de perfusion extracorporelle de foie de porc sur un modèle porc-primate.

With the increasing success of liver transplantation there is an urgent need for developing an artificial liver support system to be used in patients with liver failure. An extracorporeal porcine liver perfusion machine was successfully tested in animals with experimental liver failure. Livers were flushed, removed from 35 kg pigs and placed in a heated sterile cassette. The portal vein and the hepatic artery of the graft were connected to the arterial system of the animals. The perfusion pressure of the hepatic artery was regulated via a pressure-flow computerized feed-back device. The venous flow was reinfused from the hepatic veins of the graft to the jugular vein of the animals. The experimental work consisted in two steps: 1. evaluation of clinical and biological consequences of liver perfusion in healthy animals (Group A = pigs, n = 3; group B = primates, n = 3); 2. evaluation of the efficiency of the liver perfusion in animals with ischemic liver failure (Groupe D = pigs, n = 6). The control group (Group C = pigs, n = 7) consisted of pigs with ischemic liver failure without hepatic support. No major clinical or biological adverse effects are reported in groups A and B excepted a thrombocytmia and a marked increase in serum transaminases levels in group B. Liver function as assessed by the bile flow was good in both groups. Comatose pigs with ischemic hepatic failure (group D) recovered a subnormal neurological status in five out of six cases. Serum ammoniemia level were significantly decreased (from 1076 +/- 163 to 255 +/- 32 umol/l). A decrease in serum bilirubine levels and an improvement in the coagulation profile were observed in the perfused animals. Pigs and primates tolerated the perfusion procedure well and beneficial effects were observed in perfused pigs with experimental liver failure.

[Use of urapidil during surgery for pheochromocytoma]. / Utilisation de l'urapidil au cours de la chirurgie du phéochromocytome.

OBJECTIVE: To investigate the efficacy of urapidil, administered either by boluses or a continuous infusion, to control hypertension during resection of phaeochromocytoma. STUDY DESIGN: Prospective open study. PATIENTS: Seven consecutive patients aged between 23 and 60 years, with a hypersecretant phaeochromocytoma. METHODS: Standard anaesthetic technique including thiopentone, opioid, muscle relaxant, nitrous oxide and isoflurane. Invasive haemodynamic monitoring with a Swan-Ganz catheter and radial arterial catheterization. Infusion of cristalloids and colloids (20 mL.kg-1.h-1). Evaluation of two regimens of urapidil administration following the initial injection of a bolus of 25 mg in case of severe hypertension i.e. SAP > 180 mmHg > 1 min: a) boluses of 25 or 50 mg of urapidil injected according to the response obtained after the first bolus or in case of resurgence of a new hypertensive event; b) continuous infusion of 150-200 mg.h-1. RESULTS: Three patients developed hypertension between the induction of anaesthesia and the beginning of the tumor dissection. One bolus of 25 or 50 mg of urapidil was efficient to control this event. During the dissection of the phaechromocytoma, higher doses (75-100 mg) were required to significantly decrease SAP and DAP values (P < 0.001). Heart rate did not change significantly in patients not receiving esmolol. A continuous infusion, used in three patients, did not prevent the occurrence of peaks in two patients, requiring additional doses. After the removal of the tumor, three patients experienced severe hypotension with decreased systemic vascular resistances and high cardiac output. Vasoactive drugs were injected to restore better haemodynamic conditions. CONCLUSION: Urapidil is useful for the management of hypertension during the resection of phaechromocytoma. However further investigations are needed to determine its role in the occurrence of prolonged collapse after the tumor removal.

Concentrations in plasma and tissue penetration of ceftriaxone and ornidazole during liver transplantation.

Plasma and epiploic fat drug concentrations and fat penetration of ceftriaxone and ornidazole given for antimicrobial prophylaxis were studied in 11 patients scheduled for liver transplantation. Ceftriaxone (1 g) and ornidazole (500 mg) were infused during 30 min after the induction of anesthesia. Arterial blood and epiploic fat samples were collected at 30, 60, and 120 min and then every 90 min following the end of the infusion until closure of the peritoneum. Blood samples were immediately centrifuged, and plasma and fat were stored at -35 degrees C until analysis. Ceftriaxone and ornidazole concentrations were determined by high-performance liquid chromatography. Surgery lasted 440 +/- 84 min and required a mean of 9.5 units of packed erythrocytes and 13 units of fresh frozen plasma. Plasma ceftriaxone concentrations decreased from 89 +/- 34 to 41 +/- 16.5 micrograms/ml from the beginning of the operation until the time of closure of the peritoneum. Corresponding levels in epiploic fat decreased from 8.7 +/- 3.3 to 4.5 +/- 3.5 micrograms/g. Ornidazole concentrations ranged, respectively, between 8.7 +/- 2.5 and 4.9 +/- 1.7 micrograms/ml in plasma samples and 4.6 +/- 1.2 and 2.5 +/- 1.1. micrograms/g in fat samples. Rates of penetration into the omentum remained at about 9% for ceftriaxone and between 50 and 70% for ornidazole. Tissue ceftriaxone concentrations were, in all cases, greater than typical MICs for 90% for Escherichia coli and Klebsiella isolates tested (MIC90S). They were insufficient in 40% of patients after 60 min with regard to the MIC90S for Staphylococcus aureus. Tissue ornidazole concentrations were not superior to MIC90S for anaerobes after 30 min in 50% of patients. These results show that a single dose of 1 g of ceftriaxone provides adequate coverage against gram-negative bacteria and that 1 g instead of 500 mg ornidazole may provide a protective effect against anaerobes during liver transplantation. Prophylaxis against S. aureus and Streptococcus faecalis requires more specific antibiotics. Prophylaxis for patients with significant blood loss or initial severe renal or hepatic failure needs further evaluation.

Mixed venous oxygen saturation monitoring during liver transplantation.

High mixed venous oxygen saturation (SVO2) values due to limited oxygen extraction capacities are reported in some patients with severe liver disease. The aim of this study was to evaluate the usefulness of SVO2 monitoring to assess adequate oxygen supply in such patients scheduled for liver transplantation. Nineteen patients with oxygen extraction ratio below 12% were analysed and compared to 20 patients with a pre-operative ratio over 17%. The two groups were comparable with regard to initial pathology, preload and haemoglobin levels. SVO2 values measured discontinuously by co-oximetry were unaffected by the first part of surgery and the clamping period in patients with low oxygen extraction ratio. In these patients, SVO2 was never correlated to oxygen supply during the whole procedure whereas good correlation was noted before and after unclamping in the other group. Tissue hypoxia detected by a dependent oxygen consumption-oxygen supply relationship occurred at clamping and unclamping in patients with initial low oxygen extraction capacities. It is concluded that expensive SVO2 continuous monitoring may not be effective in reflecting changes in oxygen supply in anaesthetized patients with initial severely impaired oxygen extraction capacity.

Oesophageal thermal tube for intraoperative hypothermia in liver transplantation.

In order to prevent the occurrence of major hypothermia during liver transplantation, with its deleterious effects on intraoperative cardiovascular activity and on postoperative graft functioning, this study evaluated the benefit of an oesophageal rewarmer, used during surgery, in addition to the usual methods of warming (OR temperature at 22 degrees C, rewarming of fluids and blood, heating mattress, heat and moisture exchanger). We compared 10 patients with an oesophageal rewarmer (OeR group) to 10 patients without (Control group). The anaesthetic procedure was similar in all cases. Rectal (RT) and pulmonary artery (PT) temperatures were recorded during the three phases of surgery (pre-anhepatic, anhepatic, postanhepatic phase) and their time course was analysed with non-parametric tests. The two groups were comparable with regard to duration of surgery, blood and fluid requirements and veno-venous bypass flow rate. The RT decreased similarly in both groups, but was significantly higher in the OeR group at peritoneum closure (P < 0.01). The PT was higher in the OeR group after onset of venous shunting (P < 0.05) and during the third phase of surgery (P < 0.01). Three incidents (one leakage and two herniations of the latex tube) occurred, without detrimental effects on the patients. It is concluded that the oesophageal heat exchanger allows better rewarming after revascularization of the graft, but is unable to prevent cardiac hypothermia at unclamping.

[Problems posed by the inferior vena cava in liver transplantation]. / Problemes posés par la veine cave inférieure en transplantation hépatique.

On the basis of a 200-case series, we report about the problems posed by the inferior vena cava for liver transplantation, and about the means implemented to solve these problems. Before hepatic transplantation, agenesia of the vena cava, which was encountered once, did not prevent grafting. During transplantation, the inferior vena cava posed problems due to its size or to the approach. These were solved using an extracorporeal venovenous shunt, which we advocate to systematically use for liver transplantation. Following transplantation, in addition to hemorrhages, the problems posed by the IVC included supra- or infrahepatic anastomotic stenoses (2 cases) and infrarenal, retrohepatic or suprahepatic thromboses (2 cases). Their repair again resorted to a venovenous shunt, for which we specify the strategy of use.

[Difficult intubation managed by laryngeal mask and fibroscopy]. / Intubation difficile réglée par un masque laryngé et un fibroscope.

A case is reported of a patient due to undergo a combined kidney and pancreas transplant who proved to be difficult to intubate. This diabetic hypertensive 35-year-old male patient also had ankylosing spondylitis. Mouth opening was normal (more than fingers' breadth), the chin-sternum distance was 4 cm on full cervical flexion, and cervical extension was only slightly impaired. The Mallampati score was 1. Anaesthesia was induced with thiopentone, fentanyl and 6 mg of pancuronium. Mask ventilation was quite satisfactory. However, on laryngoscopy, the vocal cords could not be seen. Several attempts to carry out endotracheal intubation, including with a stylet, failed. A laryngeal mask (LM) was therefore applied to ventilate the patient correctly. It was not possible to pass a small endotracheal tube (6 mm diameter) through the LM tube, probably because of a small malposition of this latter. A paediatric fibroscope, passed through the LM tube, served as guide for the endotracheal tube. The mask was not removed, although its cushion was slightly deflated, so as not to extubate the patient. The benefits and usefulness of a laryngeal mask in predictable and unpredictable cases of difficult intubation are discussed.

[Hemodynamics and hepatic transplantation using a veno-venous shunt: influence of the preoperative hyperkinetic state]. / Hémodynamique et transplantation hépatique avec shunt veino-veineux: influence de l'état hyperkinétique préopératoire.

The routine use of a veno-venous bypass is not accepted by all surgical liver transplantation teams. The putative benefits (maintaining haemodynamic stability during the anhepatic phase, reducing blood losses, avoiding renal failure) are counterbalanced by the real risks of air embolism or thromboembolism. A severe preclamping hyperkinetic haemodynamic status represents an elective indication for some authors, whilst it is a reduced cardiac function for others. Two groups of ten patients undergoing liver transplantation, with a porto-femoro-axillary venous bypass (flow rate 2 to 2.5 l.min-1), were studied retrospectively. They differed by their pre-clamping cardiac index (CI), greater than 5 l.min-1.m-2 in group A and less than 4.5 l.min-1.m-2 in group B. The same anaesthetic protocol was used in all patients consisting in fentanyl, thiopentone, pancuronium, and midazolam. The use of blood products and biological parameters did not differ between the two series of patients. The CI decreased by 30% and systemic vascular resistances (Rsa) increased by 48% in group A after clamping, without any deleterious effects on oxygen delivery; similarly, in group B, CI fell by 15% and Rsa increased by 20%. After unclamping, CI rose by greater than 50%, and Rsa decreased in both groups. No differences were seen between the two series 5 min after revascularisation. The release of vasoactive agents by the cold ischaemic graft could explain this. These results suggest that veno-venous bypass could be beneficial in the 2 different preoperative haemodynamic profiles studied. The low decrease in CI in hyperkinetic patients allowed tissue oxygenation to be maintained at adequate levels during the anhepatic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion.

Propofol (mean dose 2.85 mg kg-1 h-1) was administered for 4 days by continuous i.v. infusion for sedation in 14 agitated and restless ICU patients. This provided rapid control of the level of sedation. When the infusion was discontinued, adequate recovery with response to commands was obtained in most patients by 10 min. Recovery times and the decrease in blood propofol concentration were similar after 24, 48, 72 and 96 h of infusion. Cumulative effects, tachyphylaxis, or other untoward effects were not observed.

Propofol in elderly high risk patients. A comparison of haemodynamic effects with thiopentone during induction of anaesthesia.

Twenty elderly patients of ASA grade 3 or 4, received either propofol 1 mg/kg or thiopentone 2 mg/kg for induction of anaesthesia. These doses provided a convenient level of anaesthesia for all patients. There were no significant intra- or intergroup haemodynamic changes, with the exception of a decrease in diastolic pressure and rate-pressure product after propofol. It is concluded that propofol 1 mg/kg can be used to induce anaesthesia in elderly high risk patients without deleterious cardiovascular effects.