Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR).

PURPOSE: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. METHODS: In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. RESULTS: The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). CONCLUSION: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

Porcine model of ruptured abdominal aortic aneurysm repair.

OBJECTIVES: To validate a porcine model of ruptured abdominal aortic aneurysm (rAAA) repair. DESIGN: Experimental study. METHODS: Ten experimental and five sham-operated pigs were studied. Instrumentation for cardiac output (CO) measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was visualised sublingually and in ileostoma. PROTOCOL: simulation of rAAA with bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of post-surgery care. RESULTS: Six experimental pigs completed the protocol and are presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline. From clamping on CO and PORT increased above baseline whereas REN (47%) with creatinine clearance remained compromised till the end. Microcirculation was affected more in ileum than sublingually. Approximately threefold increase in cytokines (tumour necrosis factor-α (TNF-alpha), interleukin (IL)-6 and IL-10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs) and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and TBARs was observed in sham-operated animals. Organ histology did not reveal differences between groups. CONCLUSIONS: This near-lethal model of rAAA induced expected severe deterioration of haemodynamics and metabolism accompanied with a moderate inflammatory and oxidative stress response.

Anaesthesia management of major hepatic resections without application of allogeneic blood.

BACKGROUND: In a prospective study we used acute normovolemic haemodilution (ANH) together with low CVP anaesthesia in order to avoid allogeneic blood transfusion during major liver surgery. MATERIAL AND METHODS: With institutional approval, 20 patients, ASA classification I-III, undergoing hepatic lobe resection consecutively (18 for metastatic cancer, 2 for hepatocellular cancer) in 2002, were enrolled into the prospective study. A epidural catheter was inserted before surgery in the thoracic region. General anaesthesia was induced and maintained with sevoflurane and fentanyl. Invasive haemodynamic monitoring was instituted. Blood was removed for ANH and circulation volume was replaced by infusion of colloids and crystalloid. The CVP was maintained less than 5 mm Hg during hepatic parenchymal transection. After procedure the ventilated patients were transported to ICU. RESULTS: The preoperative haematocrit value (Hct) allowed performance of ANH with a blood removal (1025 +/- 357 g) in all patients. The estimated blood loss was 825 +/- 515 ml. None of the subject received allogeneic blood during surgery. One patient had transfusion of 2 units of allogeneic blood the fifth day after the right hepatectomy during a second look for perihepatic hematoma. The CVP was 3.8 +/- 0.4 mmHg during liver resection. Postoperative Hct was 0.31 +/- 0.02 and haemoglobin 108 +/- 11 g/L. All patients were extubated the first day after surgery. There was no hospital mortality. CONCLUSIONS: We have shown that the routine use of new surgical techniques and low CVP anaesthesia in combination with ANH enabled avoidance of allogeneic blood transfusion in all patients during surgery. (Tab. 3, Ref. 22).

Intraoperative mild hypothermia therapy in patients scheduled for neurosurgical procedures.

BACKGROUND: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgicals procedures complicated by cerebral ischaemia. Our prospective study was designed to examine the safety of deliberate mild hypothermia and to evaluate our techniques for cooling and rewarming. MATERIALS AND METHODS: With institutional approval, 20 patients scheduled for elective neurosurgery were enrolled into our prospective study. After the induction of anaesthesia, the core temperature was measured by urinary catheters with probes (Kendall). The patients were cooled (temperature of blankets set at 15 degrees C) and rewarmed (temperature set at 40 degrees C) by two circulating water blankets (Blanketrol III, Cincinnati Sub-Zero, Cincinnati). The variables are expressed as a mean +/- standard deviation. RESULTS: The time of anaesthesia was 316+/-53 min. The core temperature was 36.5+/-0.4 degrees C at the start of anaesthesia. The minimal temperature reached 34.4+/-0.4 degrees C. The patients were cooled at a rate of 1.1+/-0.3 degrees C/h and rewarmed at a rate of 0.9+/-0.4 degrees C/h. The temperature was 35.8+/-0.5 degrees C after the neurosurgical procedure. Deliberate mild hypothermia with rewarming did not cause delays in emerging from anaesthesia. On the control CT scan, no ischaemic changes were observed after surgery. CONCLUSIONS: Our findings indicate that patients can be cooled and rewarmed by two circulating water blankets, and core temperatures about 34 degrees C were easily achieved. The deliberate mild hypothermia is together with careful anaesthesia management a safe technique of cerebral protection from ischaemic insult during elective neurosurgical procedures. (Tab. 1, Ref. 11.).

Acute normovolemic haemodilution for management of 4200 ml blood loss during radical prostatectomy.

BACKGROUND: We refer a case report of patient with 4200 ml large blood during urological surgery, in which was used acute normovolemic haemodilution as a solely method for avoiding of allogeneic blood transfusions. METHODS: A 65 years old patient was scheduled for radical prostatectomy. After starting general anaesthesia was removed 2360 g (target haematocrit 0.30 in patients with calculated total body blood volume 5460 ml) of whole blood from patient and circulation volume was replaced by 1500 ml of colloids and 2000 ml of crystalloid solution. Retransfusion was started after 1800 ml blood loss (transfusion trigger--Hct 0.20). RESULTS: The total blood loss was 4200 ml during 4 hour and 40 minutes of surgery. The patient was the whole operation time haemodynamic stable, with minimal systolic blood pressure 100 mmHg and haematocrit value was 0.32 after the procedure. CONCLUSIONS: To reduce the risk of anaemia and also the risk of allogeneic blood transfusion is the one of the basic part of the anaesthesia management of large urological procedures. This case demonstrated the effectiveness and safety of acute normovolemic haemodilution as a method for avoiding allogeneic blood transfusion in a patient with 77% loss of total body blood volume.

[Use of erythropoietin in radical prostatectomy]. / Pouzití erytropoetinu u radikální prostatektomie (RAPE).

All patients in the first group tolerated sampling of four transfusion units of autologous blood in the course of two weeks with subsequent erythropoietin administration very well. Erythropoietin was well tolerated, no local nor systemic undesirable side-effects or complications were observed. The mean transferrin and serum iron values remained during sampling of autotransfusions and erythropoietin administration within the range of normal values reported by our laboratory. The ferritin levels were above the norm. On the other hand in patients of the control group it was not possible--due to the decline of haemogram values--to sample in 45% the required amount of autologous blood before operation. For the same reason it was not possible to implement haemodilution as required. In similar blood losses administration of allogenic blood was necessary in 35% patients of the control group whereby in the group of patients with erythropoietin allogenic blood was administered in two cases (10%). Erythropoietin administration can effectively facilitate preoperative sampling of autotransfusion within a relatively short period. By its administration we can prevent a marked decline of red blood cells as a result of sampling of several preserves of autologous blood at a rapid rate. A satisfactory value of the haematocrit before the operation proper moreover makes it possible to collect a larger amount of blood in case of acute isovolaemic haemodilution. This enhances the patient's safety in relation to risks ensuing from administration of allogenic blood.

[Indications for laparoscopic adrenalectomy]. / Indikace k chirurgické laparoskopické adrenalektomii.

Endocrinological indication for surgical adrenalectomy is relatively rare. There is relatively little information on possibilities how to perform adrenalectomy by a minimally invasive procedure. Minimal invasive surgery made it possible to implement some operations sparing the patient. Adrenalectomy is one of these procedures. Laparoscopic adrenalectomy, which is extremely rare in other countries, as practiced in the Czech Republic, is the subject of the submitted paper.

[Thoracoscopy in upper thoracic sympathectomy]. / Torakoskopická horní hrundní sympatektomie.

The authors describe their experience with the endoscopic technique of upper thoracic sympathectomy. They evaluate it as an easily performed and safe method which gives great comfort to the patient as well as excellent functional and cosmetic results and involves a minimal burden and ensures rapid convalescence. It enables the surgeon to obtain a perfect orientation in the surgical field as well as safe and perfect preparation of the thoracic portion of the sympathetic nerve. The low cost is also important.

[Angiotensin converting enzyme inhibitors in controlled hypotension during spinal surgery]. / Inhibitory angiotenzin konvertujícího enzymu v rízené hypotenzi behem spondylochirurgických výkonu.

BACKGROUND: Controlled hypotension is an advantage during spondylosurgical operations: the objective is to achieve a mean arteriae pressure of 8 kPa (60 mm Hg). The most frequently used 0.01% solution of sodium nitroprusside must be increased in some patients to amounts which involve the risk of intoxication. This applies to patients with an increased sympathoadrenal activity and ready mobilization of the renin-angiotensin system. The objective of the present investigation was to test the inhibitor of the angiotensin converting enzyme in hypotension controlled by nitroprusside. METHODS AND RESULTS: To twenty patients before a spondylosurgical operation as premedication angiotensin converting enzyme inhibitor (ACE)--captopril--was administered, 25 mg by the oral route. The control group was formed by 20 patients with spondylosurgery under controlled hypotension with nitroprusside administration. The effect of captopril was manifested by a reduced amount of nitroprusside needed to maintain the median pressure of 8 kPa; in the captopril group 1.073 +/- 0.52 microgram.kg-1.min-1 was used, as compared with 1.786 +/- 1.04 micrograms.min-1 in the control group (p < 0.01). Concurrently monitored values of plasma renin activity were higher in the patients given captopril: 7.352 +/- 5.75 nmol.l-1, as compared with 5.583 +/- 3.73 nmol.l-1 (p < 0.05). CONCLUSIONS: Premedication with ACE inhibitor (captopril), even when administered in small doses via p. o., reduced the sodium nitroprusside consumption by as much as 60%. The elevated plasma renin values were objective evidence of the effect of captopril.

[Impossibility of artificial ventilation in a prone position in a patient with deformity of the spine (case-history).]. / Znemoznení umelé plicní ventilace pronacní polohou u nemocné s deformitou pátere.

The authors present the case of a 15-year-old female patient (Jehova's Witness) who was operated at the age of two on account of a Wilms' tumour of the kidney and irradiated with subsequent postirra-diation scoliosis. In 1990-1993 she was six times subjected to anaesthesia for distraction with a Harrington rod and repeated redistractions. All anaesthesias were of the general type, with artificial pulmonary ventilation in the prone position and without complications. Anaesthesiological methods and procedures were used which made it possible to avoid administration of blood or blood derivatives. In March 1993 the patient was prepared with erythropoietin for the final treatment of the deformed spine. During general anaesthesia suddenly artificial pulmonary ventilation in a prone position became impossible due to complete collapse of the trachea closely behind the end of the armed tracheal tube. After postponing the procedure, bronchoscopic and CT examination in a supine position during spontaneous respiration confirmed stenosis of the distal portion of the trachea to one third of the lumen. The authors assume that the cause are altered anatomical relations of the mediastinum caused by distraction and repeated redistractions in a field affected by irradiation. Key words: deformity of the spine, stenosis of the trachea, Jehova's Witnesses.

[Initial experience with peroperative autotransfusion in spinal surgery]. / První zkusenosti s peroperacní autotransfúzí ve spondylochirurgii.

The authors describe combinations of anaesthesiological methods which enabled them during extensive spondylosurgical operations in 66 patients to reduce the consumption of homologous blood during operation to 90 ml, on the first day after operation to 300 ml and on the second day after operation to 120 ml. In six patients they used preoperative collection of the patient's own blood, in 45 patients acute normovolaemic haemodilution, in all patients controlled hypotension with sodium nitroprusside to a mean arterial pressure of 8-9 kPa and peroperative collection of blood by means of an autotransfusion apparatus Dideco Stat with a standard programme and yield higher than 50%. During and after peroperative collection they did not record any complications. Lower haemoglobin and haematocrit values and a reduced number of erythrocytes, lower than the lower normal range, during and after operation did not threaten the postoperative course in these patients. The authors draw, however, attention to the rise of the number of leucocytes immediately after operation to 19.7 x 10(9). 1(-1) which is due to their shift into the final product. Solution of this phenomenon which can produce ARDS is according to the authors the use of a programme different from the standard one.

[The effect of controlled hypotension on kidney function in spinal surgery]. / Vliv rizené hypotenze pri operacich pátere na funkci ledvin.

The authors investigated the influence of controlled hypotension on renal function in patients operated on account of idiopathic scoliosis of the spine. The deformity was corrected by posterior fusion with Harrington instrumentation under general anaesthesia during controlled hypotension induced by sodium nitroprusside (n = 20). The control group was formed by 20 patients with the same deformity and the same surgical procedure without hypotension. The renal function was assessed before operation, during operation and continuously for 102 hours after operation. In the group of patients with controlled hypotension (median arterial pressure 8.0 kPa) during operation a significant decline of the creatinine clearance occurred (0.7 ml/s), as compared with the control group (1.3 ml/s), as well as compared with the value before operation (1.7 ml/s). After terminated hypotension the mean value of creatinine clearance rose to 2.0-2.2 ml/s for a period of 42 hours. In the control group the creatinine clearance persisted at a slightly reduced level, recorded during operation, for another 30 hours. Sodium retention as a manifestation of hyperaldosteronism was less marked in patients with controlled hypotension. During the investigation period no biochemical signs of retention of nitrogenous substances were recorded.

[The effect of controlled hypotension during spinal surgery on kidney function]. / Der Einfluss der kontrollierten Hypotension bei Wirbelsäulenoperationen auf die Nierenfunktion.

The effect of controlled hypotension on renal function in patients operated on for idiopathic scoliosis of the spine was examined (n = 20). The deformity was corrected under general anesthesia by posterior fusion using Harrington's instrumentation during controlled hypotension induced by sodium nitroprusside. The control group included 20 patients suffering the same deformity and operated on in the same way but without hypotension. Renal function tests were performed before and during the operation and continuously for 102 h after surgery. In the group with controlled hypotension (medium arterial pressure 8.0 kPa) there was a significant decrease in creatinine clearance during the operation (0.70 ml/s) compared with that in the control group (1.30 ml/s) and with the value before surgery (1.70 ml/s). At the end of hypotension, the average clearance value of creatinine increased up to 2.0-2.2 ml/s within 42 h. In the group of control patients (medium arterial pressure 11.5 kPa) the creatinine clearance persisted at a mildly decreased level (1.3 ml/s) during surgery and for a further 30 h after. The sodium retention characteristic of hyperaldosteronism was less marked in the patients with controlled hypotension. We did not observe any biochemical findings indicating retention of nitro substances. Controlled hypotension induced by sodium nitroprusside at surgical treatment of the vertebral column does not cause any impairment of the renal function either during surgery or as a late sequela.