Changes in calcitonin gene-related peptide, atrial natriuretic peptide and brain natriuretic peptide in patients undergoing coronary artery bypass grafting.

The initiation of cardiopulmonary bypass creates significant derangements in cardiovascular volume status and both endocrine and autonomic nervous system function. To examine whether such derangements might differ in patients with different pre-operative physical status scores, we measured the plasma concentrations of calcitonin gene-related peptide, atrial natriuretic peptide and brain natriuretic peptide, catecholamines and antidiuretic hormone, as well as haemodynamic variables, during and after cardiopulmonary bypass in 27 consecutive patients undergoing coronary artery bypass grafting. The pre-operative levels of atrial natriuretic peptide and brain natriuretic peptide differed significantly between ASA II patients and III and IV patients [mean (SD) brain natriuretic peptide levels = 14 (8.2) vs. 129 (51) pg.ml-1]. Plasma calcitonin gene-related peptide increased significantly in both groups after the initiation of cardiopulmonary bypass, and remained increased throughout cardiopulmonary bypass. The changes in plasma epinephrine, norepinephrine and antidiuretic hormone were similar to those reported previously. The changes in plasma calcitonin gene-related peptide, atrial natriuretic peptide and brain natriuretic peptide did not correlate with any changes in haemodynamic variables before or after cardiopulmonary bypass. Measurement of plasma brain natriuretic peptide might usefully be included in the pre-operative evaluation of patients with cardiac disease.

Effects of cholinomimetic injection into the brain stem reticular formation on halothane anesthesia and antinociception in rats.

The brain stem reticular formation plays an important role in determining consciousness and arousal. Modulation of cholinergic neurotransmission in this region alters the sleep-wake cycle. In the present study, we examined the effect of the direct application of cholinergic agents into the pontine reticular nucleus on anesthetic requirements and recovery and antinociception in rats. Sprague-Dawley rats were implanted with 24-gauge guide cannulas 1.0 mm above the oral portion of pontine reticular nucleus (PnO) while under pentobarbital anesthesia with the use of a stereotaxic apparatus. After recovery from surgery, animals were randomly assigned to one of the following protocols: minimum alveolar concentration (MAC), recovery time, tail-flick latency, or motor blockade. All measurements were performed after carbachol microinjection into the PnO after pretreatment with atropine or mecamylamine. Carbachol injection into the PnO significantly reduced MAC of halothane and prolonged recovery in a dose-dependent manner. Pretreatment with atropine reversed MAC reduction by carbachol, and both atropine and mecamylamine shortened recovery time under carbachol. In unanesthetized rats, carbachol produced antinociceptive effects as reflected by a change in tail-flick latency response. Atropine and mecamylamine inhibited antinociceptive effects of carbachol. These results suggest that cholinomimetic injection into the PnO modulates the anesthetic state produced by halothane, suggesting participation of this area in the mechanisms in the brain that generate the anesthetic state.

Antinociception by epidural and systemic alpha(2)-adrenoceptor agonists and their binding affinity in rat spinal cord and brain.

UNLABELLED: This study was designed primarily to relate the antinociceptive and hemodynamic effects of clinically available alpha(2)-adrenoceptor agonists to their binding affinity for alpha(2)-adrenoceptors in the spinal cord and brain. In rats with chronic indwelling epidural catheters, the percentage maximal possible effect on tail-flick latency was measured after epidural or IM dexmedetomidine (DXM), clonidine (CL), or tizanidine (TZ) administration. To examine their binding affinities, isolated spinal cord and brain membranes with an alpha(2) agonist were incubated with (3)H-UK14304, a selective alpha(2) agonist, and the radioactivity in the reaction mixtures was measured by liquid scintillation spectrometry. Epidural DXM (0.5-10 microg), CL (10-500 microg), and TZ (5-500 microg) all produced dose-dependent antinociceptive effects; the rank order of potencies was DXM > CL > TZ, the same as for their systemic administration. The antinociceptive effects were blocked by epidural yohimbine. The receptor binding affinities expressed as the concentration that inhibits 50% for spinal cord and brain, respectively, were 0.25 and 1.3 nM (DXM), 10.8 and 12.5 nM (CL), and 48.2 and 96.8 nM (TZ). The changes in arterial blood pressure and heart rate evoked by antinociceptive doses did not correlate with the rank order of antinociceptive potencies. The relative antinociceptive potencies of epidural alpha(2) agonists may depend on their binding affinities to alpha(2)-adrenoceptors in the spinal cord, but their cardiovascular effects may result from actions both inside and outside the central nervous system. IMPLICATIONS: Spinal antinociception caused by the epidural administration of alpha(2) agonists is well correlated with their binding affinity to spinal alpha(2)-adrenoceptors.

Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) suppress various hyperalgesia perhaps via inhibition of cyclooxygenase activity at the spinal cord. The present study aimed to examine whether epidural application of NSAIDs affects hyperalgesia induced by nitric oxide. METHODS: The authors studied the antinociceptive effects of epidurally administered NSAIDs in rats with a chronically in-dwelling epidural catheter by three hyperalgesic models, including nitric oxide-induced hyperalgesia by nitroglycerin (10 microg) or l-arginine (100 microg), and the biphasic response in the formalin test. RESULTS: Epidural, but not systemic, nitroglycerin induced hyperalgesia that was completely blocked by methylene blue but not by N(omega)-nitro-L-arginine methyl ester (L-NAME). Epidural l-arginine, but not d-arginine, also induced hyperalgesia that was completely blocked by L-NAME. Epidural S(+)ibuprofen (100-1,000 microg) suppressed the nitroglycerin- and l-arginine-induced thermal hyperalgesia and also the second phase response in the formalin test. Neither systemic S(+)ibuprofen nor epidural R(-)ibuprofen suppressed the hyperalgesia Epidural indomethacin (10-100 microg) or diclofenac (10-1,000 microg) dose-dependently suppressed nitroglycerin-induced thermal hyperalgesia The order of potency for this suppression (ID50 in microg) was indomethacin = didofenac > S(+)ibuprofen >> R(-)ibuprofen. CONCLUSIONS: The antinociceptive action of epidurally administered NSAIDs could be the result of suppression of spinal sensitization, perhaps induced with nitric oxide in the spinal cord. The ID50 values for epidural indomethacin, diclofenac, and S(+)ibuprofen were about 10 times higher than those reported in other studies for intrathecal NSAIDs in hyperalgesia models. (Key words: Cyclooxygenase inhibitors; NO donor; NO precursor; optical isomers; neuroplasticity.)

Spinal antinociceptive action of Na+-K+ pump inhibitor ouabain and its interaction with morphine and lidocaine in rats.

BACKGROUND: The Na+,K+-adenosine triphosphatase is a ubiquitous enzyme system that maintains the ion gradient across the plasma membrane of a variety of cell types, including cells in the central nervous system. We investigated the antinociceptive effect of intrathecally administered ouabain and examined its potential interaction with spinal morphine and lidocaine. METHODS: Using rats chronically implanted with lumbar intrathecal catheters, the ability of intrathecally administered ouabain, morphine, and lidocaine and of mixtures of ouabain-morphine and ouabain-lidocaine to alter tail-flick latency was examined. To characterize any interactions, isobolographic analysis was performed. The effects of pretreatment with intrathecally administered atropine or naloxone also were tested. RESULTS: Intrathecally administered ouabain (0.1-5.0 microg), morphine (0.2-10.0 microg), and lidocaine (25-300 microg) given alone produced significant dose- and time-dependent antinociception, but systemic administration of ouabain did not produce such an effect. The median effective dose (ED50) values for intrathecally administered ouabain, morphine, and lidocaine were 2.3, 5.0, and 227.0 microg, respectively. Isobolographic analysis exhibited a synergistic interaction after the coadministration of ouabain and morphine. With ouabain and lidocaine, there was no such evidence of synergism. Intrathecally administered atropine, but not naloxone, completely blocked the antinociceptive effect of ouabain and attenuated its interaction with spinally administered morphine. CONCLUSIONS: Intrathecally administered ouabain produces antinociception, at least in part, via an enhancement of cholinergic transmission in the spinal nociceptive processing system. The results of the interaction of ouabain with morphine and lidocaine suggest that modulation of Na+-,K+-electrochemical gradients and thus subsequent release of neurotransmitters in the spinal cord are likely to play important roles in the spinal antinociceptive effect of intrathecally administered ouabain.

[Hemorrhagic shock during laparoscopic cholecystectomy detected by transesophageal echocardiography].

A 47-year-old man was scheduled for laparoscopic cholecystectomy under general anesthesia supplemented with epidural anesthesia. A direct arterial line and a transesophageal echocardiogram probe were inserted before surgery. Anesthesia was maintained with nitrous oxide and isoflurane but without epidural anesthesia. Severe hypotension occurred about 30 minutes after introducing pneumoperitoneum but surgeons denied massive bleeding in the operative field. Although this made us difficult to diagnose the incident as massive bleeding or pulmonary air embolism (PAE), a collapsed heart was detected by transesophageal echocardiography (TEE). Its end-diastolic diameter of the left ventricle was reduced to 20 mm and left ventricular end-systolic cavity obliteration was demonstrated. We could easily diagnose the decrease of blood volume due to PAE using TEE.

Prediction of patients with higher order multifetal pregnancy at risk for postpartum pulmonary edema.

OBJECTIVE: This retrospective study aims to verify the factors for the development of maternal pulmonary edema in higher order multifetal pregnancy. STUDY DESIGN: We analyzed medical profiles of a total of 13 triplet, quadruplet and quintuplet pregnancies for the years 1992 through 1997. Some treatments were applied in attempts to promote these multifetal pregnancies. All underwent cesarean section, two of which developed pulmonary edema within a few hours of delivery. There had been no evidence for the development of pulmonary edema antepartum. RESULTS: In the patients affected by pulmonary edema, postoperative values of PaO2/FIO2<250 mmHg showed close association to a value perioperative fluid loading index (FLI)>0; the index consists of an intraoperative fluid balance and preoperative infusion volume within 24 h prior to surgery. Two patients with postoperative pulmonary edema had a perioperative FLI>0, whereas the others had values 0 may have a much higher risk for postoperative pulmonary edema, suggesting the predictive role of the perioperative FLI value.

Pulmonary arterial and right ventricular responses to prophylactic albumin administration before aortic unclamping during abdominal aortic aneurysmectomy.

UNLABELLED: During abdominal aortic aneurysmectomy (AAAectomy) and before aortic unclamping (XU), we studied the effects of albumin administration on pulmonary arterial and right ventricular responses in 39 anesthetized patients using a modified thermodilution technique. Group 1 patients (n = 18) were given no extra IV fluids. Group 2 patients (n = 21) were given additional albumin administration (5% albumin at 10 mL/kg) before XU. After XU, mean arterial blood pressure (MAP) decreased significantly in each group, and MAP and stroke volume index (SVI) were not significantly higher in Group 2 than in Group 1. At 5 min after XU, the patients in Group 2 had a higher mean pulmonary arterial pressure and pulmonary vascular resistance index and a lower right ventricular ejection fraction than those in Group 1 (P < 0.05), but their SVIs were well maintained. These results indicate that albumin administration before XU may not always prevent post-XU hypotension. It caused a significant increase in right ventricular afterload and a significant dilation of the right ventricular cavity; however, right ventricular function was almost equally maintained in both groups. However, because SVI did not increase in some patients (Group 2) with the increase in right ventricular end-diastolic volume index after XU, albumin administration should be performed carefully before XU during AAAectomy. IMPLICATIONS: We studied the effects of albumin administration before aortic unclamping on pulmonary arterial and right ventricular responses during abdominal aortic aneurysmectomy using a modified thermodilution technique. Albumin administration before aortic unclamping may not always prevent hypotension, and it may cause a higher pulmonary arterial pressure than in patients without albumin administration.

[Difficult tracheal intubation with von Recklinghausen disease].

We experienced a case of difficult tracheal intubation in a 15-year-old boy with von Recklinghausen disease scheduled for resection of a right neck tumor. His scoliosis made it difficult to intubate and to manage airway because he easily developed dyspnea. We tried nasotracheal intubation with the patient awake under sedation using a bronchofiberscope, but we found an unexpected tumor jeopardizing his airway patency near his vocal cord. Preoperative examination of a tumor in the airway is essential in the anesthetic management of the patients with von Recklinghausen disease.

[Anaphylactic shock associated with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine].

A 28 year-old male patient developed anaphylactic shock on separate occasions, possibly due to the contact with a central venous catheter impregnated with chlorhexidine and silver sulfadiazine. He was successfully resuscitated. On the second operation, blood basophils disappeared and plasma histamine level increased extremely up to 80 ng.ml-1 soon after anaphylactic shock. One year after the first shock, he did not develop anaphylactic shock following the insertion of a central venous catheter without the impregnation. Pin prick test and scratch test showed positive reactions only to chlorhexidine. Latex-specific anti-IgE antibody was not detected. Therefore, chlorhexidine was confirmed as the causative agent of anaphylactic shock. Because chlorhexidine is extensively used as an antiseptic drug in emergency rooms and intensive care units, we should be aware of the possibility of chlorhexidine induced anaphylactic reactions.

Alteration of redox state of human serum albumin in patients under anesthesia and invasive surgery.

Human serum albumin is a mixture of mercapt- (HMA, reduced form) and nonmercaptalbumin (HNA, oxidized form). We studied the mercapt<-->nonmercapt conversion of human serum albumin, which reflects the redox state of the extracellular fluids, in cardiac and other common surgical_ patients using high-performance liquid chromatography. Mean values of [(HMA)/(HMA+HNA)]+/-standard deviation, fHMA+/-sigma], for patients who received common surgery (group 1) and cardiac surgery (group 2) at the start of anesthesia were 0.636+/-0.050 (n = 83) and 0.615+/-0.062 (n = 14), respectively. fHMA values were markedly lower than those for healthy male adults of 0.750+/-0.028 (n = 28). fHMA values increased at 24 h after the start of anesthesia and decreased on the 4th postoperative day in most of the patients. These postoperative changes were prominent in cardiac surgical patients. Although fHMA values after the 7th postoperative day recovered to those at the start of anesthesia in almost all of common surgical patients, those in cardiac surgical patients never recovered even on the 21st postoperative day.

Effects of blood glucose changes and physostigmine on anesthetic requirements of halothane in rats.

BACKGROUND: Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. METHODS: In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). RESULTS: In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. CONCLUSIONS: Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.

[A case of leukocytosis after massive blood transfusion for postpartum hemorrhagic shock].

We experienced the perioperative management of a hemorrhagic shock associated with postpartum uterine rupture. After the emergency abdominal total hysterectomy, massive blood transfusion was required to maintain the hemodynamics and the laparotomy for hemostasis was performed on the 1st, 2nd and 7th ICU day. Total amount of transfused blood products was 37,000 ml during one week. The patient immediately developed DIC and acute renal failure. Laboratory data showed increased leukocyte count (the peak value was 56,100 microliters-1 on the 12th ICU day), and neutrophilic fraction was more than 90% of leucocyte. After the decrease in CRP, the decrease in total bilirubin concentration was delayed. There were no other signs of infection and no remarkable change in MOF score. There was a discrepancy between this leukocytosis and the severity of organ dysfunction, and the cause of the leukocytosis was unknown.

[Bronchospasm due to anaphylactic reaction to Hydroxyethyl starch (HESPANDER)].

A 14-year-old male without any history of allergic disorders developed severe bronchospasm with skin rash 15 min. after the administration of hydroxyethyl starch (HES) during thoratic epidural anesthesia supplemented with N2O-sevoflurane-O2 anesthesia. Aminophylline, hydrocortisone, and epinephrine were administered. These treatments were effective, and the airway pressure was restored to normal ranges within 3 hrs. After the operation, the patient was extubated, because the results of the arterial blood gas examinations recovered to normal ranges. Plasma histamine and complement levels were almost within normal limits, but IgE levels were approximately 5 times higher than normal. Subsequent immediate skin test with hydroxyethyl starch showed an immunologically positive response. These results demonstrate evidence that an anaphylactic reactions could occur just after the start of HES infusion. Severe adverse reactions to HES are very rare, but it is important to keep the possibility always in mind.

The inhibitory effects of local anesthetics on superoxide generation of neutrophils correlate with their partition coefficients.

Lidocaine and tetracaine suppress superoxide anion (O2-) generation of neutrophils. We examined the effects of eight local anesthetics on O2- generation in human neutrophils and searched for a potential relationship between the biological activities and the physicochemical properties of presently available eight local anesthetics. Human neutrophils incubated with local anesthetic and a Cypridina luciferin analog as a O2(-)-specific chemiluminescence probe were stimulated by phorbol ester. The chemiluminescence development based on O2- generation was monitored by a luminometer. All of the tested local anesthetics suppressed O2- generation in a concentration-dependent manner. The concentration of each of eight local anesthetics that produced 50% inhibition of peak chemiluminescence (IC50) had a rank order of dibucaine < tetracaine < bupivacaine < ropivacaine < procaine < mepivacaine < lidocaine = prilocaine. A linear relationship was obtained between IC50 values and the values of logarithm of partition coefficient (log P) of eight local anesthetics; log (IC50 in molarity) = -1.252 - 0.514 x log P, r2 = 0.891, P < 0.001. Unlike with staurosporine, which inhibits protein kinase C (PKC), no effect was observed on the O2- generation in the presence of tetrodotoxin (TTX), veratridine (VTD), or amiloride. These results suggest that the inhibitory effects of local anesthetics on O2- generation of neutrophils are predicted by physicochemical properties of the drugs, especially partition coefficients.

[Nicorandil, as ATP-sensitive K+ channel opener, potentiated morphine analgesia].

Recent reports demonstrated that K+ channels could contribute to signal transmission in the brain and spinal cord, and opioids' action may be related to K+ channels' functions. We investigated the antinociceptive effect of epidurally injected ATP-sensitive K+ channel opener, nicorandil, using tail flick test in rats. Epidural nicorandil (100 micrograms.rat-1) increased % maximum possible effect (%MPE) of epidural morphine (1, 10 micrograms.rat-1) from -3% to 40% (P < 0.05) and 46% to 65%, respectively. Epidural glibenclamide (10 micrograms.rat-1), ATP-sensitive K+ channel blocker, antagonized this effect. Epidural nicorandil alone (10 approximately 100 micrograms.rat-1) showed no antinociceptive effects. Systemic nicorandil (100 micrograms.rat-1, i.m.) did not increase the epidural morphine analgesia. These data suggest that the K+ channel opener could point the way to a new approach to pain treatment.

[Prostaglandin E1 at low-doses improved right ventricular ejection fraction in anesthetic management for CABG].

A 52-year-old male for CABG developed a severe right heart failure, because of the direct injury to the right ventricular wall, after cardiopulmonary bypass. The volume loading therapy could not improve the cardiac function, then we used an infusion of low-dose prostaglandin E1 (0.02-0.04 micrograms.kg-1.min-1) for the acute right heart failure with increased pulmonary vascular resistance. After continuous infusion of this dose, the pulmonary vascular resistance decreased quickly, the right ventricular ejection fraction increased, and the stroke volume index also improved. These hemodynamic changes are the result of the potent vasodilating effect of PGE1, that especially could decrease selectively the pulmonary vascular resistance, and increase the preload of the left ventricle. This dose of PGE1, did not cause a severe systemic hypertension that is a serious complication during vasodilating therapy with any vasoactive drugs. In the present case, we speculated that the low-dose PGE1, is effective to improve the right ventricular function during the acute right heart failure which resulted from the intrinsic right ventricular dysfunction.

[Anesthetic management of a patient with renal cell carcinoma extending into the right atrium].

A 60-year-old man with renal cell carcinoma extending through inferior vena cava into the right atrium was scheduled for the removal of the right kidney under general anesthesia and the cardiopulmonary bypass technique. In order to obtain a clear operative field and to minimize the risk for pulmonary embolism of necrotizing tumor, total circulatory arrest under profound hypothermia (20 degrees C) was performed. Anesthesia was maintained with high doses of fentanyl (62 micrograms.kg-1), midazolam and supplemented with enflurane. We attempted to prevent circulatory collapse due to acute pulmonary embolism by tumor fragments during operation. The body temperature of the patient was decreased down to 20 degrees C for protecting central nervous system with the minimal damage. No complications occurred during anesthesia and the post-operative period. For the safe anesthetic management of the patient such as our case, adequate monitoring of circulation and protection of central nervous system are essential.

[Intraoperative acute myocardial infarction during total gastrectomy under general anesthesia combined with thoracic epidural anesthesia].

A 61-year-old, 54-kg man with gastric cancer was scheduled for total gastrectomy under general anesthesia combined with thoracic epidural anesthesia. Approximately 20 minutes after the start of the operation, the patient developed sudden hypotension and ventricular fibrillation. The cardiac rhythm returned to normal after 38 minutes of cardiopulmonary resuscitation. The operation was discontinued and the patient was transferred to an intensive care unit. A 12-lead electrocardiogram (ECG) revealed complete right bundle branch block and elevation of the ST-segment from leads II, III, aVF, V1, and V2 which indicated an inferior myocardial infarction. Laboratory data showed elevated levels of enzymes such as glutamic oxaloacetic transaminase (495 IU.l-1), lactic dehydrogenase (1781 IU.l-1), and creatine kinase-MB (112 IU.l-1). The mildly elevated levels of the enzymes decreased around 10 hours after the termination of the operation, but they increased markedly again without any change in ECG on the second postoperative day. Elevation in serum myoglobin and glutamic pyruvic transaminase and decline in arterial ketone body ratio were also detected. Furthermore, renal failure developed with increase in blood urea nitrogen and creatinine. Because of hepatic failure and renal failure which might have been caused by rhabdomyolysis, the patient needed inotropic support with dopamine, dobutamine, and epinephrine to maintain the circulation. The patient died of reinfarction of the 20th postoperative day despite intensive care such as intraaortic balloon pumping, hemodiafiltration, and continuous intravenous infusion of prostaglandin E1.