The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection.

There is conflicting evidence whether allogeneic blood transfusion influences survival or cancer recurrence after resection of hepatocellular cancer. We followed up 1469 patients who had undergone hepatocellular resection for a median (IQR [range]) of 45 (21-78 [0-162]) months, of whom 626 (43%) had had blood transfusion within 7 days of surgery. Both disease-free survival and patient survival were measured using a proportional hazards regression model and inverse probability of treatment weighting. We used restricted cubic splines for the association of the number of packed red blood cell units transfused with cancer recurrence and survival. We found that peri-operative blood transfusion was independently associated with survival and cancer recurrence after resection of hepatocellular carcinoma. Adjusted hazard ratios (95%CI) for the association of blood transfusion with cancer recurrence and all-cause mortality were 1.3 (1.1-1.4) and 1.9 (1.6-2.3), p < 0.001 for both. With more units transfused cancer recurrence was more likely and survival was shorter. The association of the number of transfused units was non-linear for cancer recurrence and linear response for all-cause mortality.

Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation.

BACKGROUND: The non-linear mixed amount with zero amounts response surface model can be used to describe drug interactions and predict loss of response to noxious stimuli and respiratory depression. We aimed to determine whether this response surface model could be used to model sedation with the triple drug combination of midazolam, alfentanil and propofol. METHODS: Sedation was monitored in 56 patients undergoing gastrointestinal endoscopy (modelling group) using modified alertness/sedation scores. A total of 227 combinations of effect-site concentrations were derived from pharmacokinetic models. Accuracy and the area under the receiver operating characteristic curve were calculated. Accuracy was defined as an absolute difference <0.5 between the binary patient responses and the predicted probability of loss of responsiveness. Validation was performed with a separate group (validation group) of 47 patients. RESULTS: Effect-site concentration ranged from 0 to 108 ng ml-1 for midazolam, 0-156 ng ml-1 for alfentanil, and 0-2.6 µg ml-1 for propofol in both groups. Synergy was strongest with midazolam and alfentanil (24.3% decrease in U50, concentration for half maximal drug effect). Adding propofol, a third drug, offered little additional synergy (25.8% decrease in U50). Two patients (3%) experienced respiratory depression. Model accuracy was 83% and 76%, area under the curve was 0.87 and 0.80 for the modelling and validation group, respectively. CONCLUSION: The non-linear mixed amount with zero amounts triple interaction response surface model predicts patient sedation responses during endoscopy with combinations of midazolam, alfentanil, or propofol that fall within clinical use. Our model also suggests a safety margin of alfentanil fraction <0.12 that avoids respiratory depression after loss of responsiveness.

Discriminant analysis for anaesthetic decision-making: an intelligent recognition system for epidural needle insertion.

BACKGROUND: Incorrect placement of epidural catheters causes medical complications. We used linear discriminant analysis (LDA) to develop an intelligent recognition system (i-RS) in order to guide epidural placement and reduce physician error. METHODS: We analysed real-time dual-wavelength fibreoptic data recorded from the end of an epidural needle in a live porcine model. Two categories of tissue layers were necessary for correct placement of catheter: epidural space and ligamentum flavum. The data were tested using linear, quadratic and logistic parametric analysis to identify which method could distinguish the two anatomical structures. RESULTS: LDA was the best fit for our model. There was ∼80% sensitivity and specificity for correct anatomical identification. Error rates based on cross-validation were 17.0% for the epidural space and 18.6% for ligamentum flavum. Error rates were greater with the 532 nm compared with 650 nm wavelength. CONCLUSIONS: The sensitivity and specificity of LDA for identifying the correct anatomical structure was similar to a physician who is an expert in epidural placement. Overall performance of an i-RS could be improved by expanding the database for decision-making and adding a category of uncertainty. This would reduce complications caused by incorrect epidural placement.

Item analysis for the written test of Taiwanese board certification examination in anaesthesiology using the Rasch model.

BACKGROUND: On the written test of board certification examination for anaesthesiology, the probability of a question being answered correctly is subject to two main factors, item difficulty and examinee ability. Thus, item analysis can provide insight into the appropriateness of a particular test, given the ability of examinees. METHODS: Study subjects were 36 Taiwanese examinees tested with 100 questions related to anaesthesiology. We used the Rasch model to perform item analysis of questions answered by each examinee to assess the effects of question difficulty and examinee ability using a common logit scale. Additionally, we evaluated test reliability and virtual failure rates under different criteria. RESULTS: The mean examinee ability was higher than the mean item difficulty in this written test by 1.28 (sd=0.57) logit units, which means that the examinees, on average, were able to correctly answer 78% of items. The difficulty of items decreased from 4.25 to -2.43 on the logit scale, corresponding to the probability of having a correct answer from 5% to 98%. There were 60 items with difficulty lower than the least able examinee and seven difficult items beyond the most able one. The agreement of item difficulty between test developers and our Rasch model was poor (weighted kappa=0.23). CONCLUSIONS: We demonstrated how to assess the construct validity and reliability of the written examination in order to provide useful information for future board certification examinations. The study was approved by the institutional review board with the following trial registered number: VGHIRB No. 97-08-14A.

A paraspinal abscess following spinal anaesthesia for caesarean section and patient-controlled epidural analgesia for postoperative pain.

We present a rare case in which a healthy parturient developed a paraspinal abscess after spinal anaesthesia for caesarean section and epidural analgesia for postoperative pain management. The catheter was in situ for 58 h. Backache was the initial and major symptom. A concealed course with no neurological deficit resulted in a delayed diagnosis and treatment in this case. The infection was not diagnosed until 20 days after the removal of the epidural catheter when there was a purulent discharge from the epidural puncture site. Surgical drainage was required. Anaesthesiologists should be aware that serious epidural analgesia-related infections can happen in extra spinal-epidural spaces. Vigilance for these infections, especially in postpartum patients with backache, is needed.

Differential effects of prazosin and yohimbine on fentanyl-induced muscular rigidity in rats.

Whereas muscular rigidity is a well-known phenomenon that is related to anesthesia induced by large doses of narcotic drugs, the precise underlying mechanism(s) remain to be fully elucidated. This study investigated the possible role of noradrenergic neurotransmission and the participation of alpha-adrenoceptors in this phenomenon. Male Sprague-Dawley rats, under ketamine-induced anesthesia (120 mg/kg, i.p.) and with proper control of respiration, body temperature and end-tidal CO2 were used. Intravenous administration of fentanyl (100 micrograms/kg) consistently caused a significant increase in the electromyographic (EMG) activity, recorded from both gastrocnemius and abdominal rectus muscles. This implied muscular rigidity was markedly antagonized by pretreatment with the specific alpha 1-adrenoceptor blocker, prazosin (50 or 250 micrograms/kg, i.v.). This antagonism occurred in spite of a high level of fentanyl in the plasma, as determined by radioimmunoassay. The specific alpha 2-adrenoceptor blocker, yohimbine (1.15 or 2.3 mg/kg, i.v.), on the other hand, not only failed to prevent fentanyl-induced activation of the EMG, but actually potentiated the response. It is concluded that noradrenergic neurotransmission, possibly originating from the locus coeruleus, may participate in the elicitation of muscular rigidity by fentanyl. Furthermore, this process may involve an excitatory action through alpha 1-, and an inhibitory action through alpha 2-adrenoceptors, in the spinal cord.

Antagonization of fentanyl-induced muscular rigidity by neurotensin at the locus coeruleus of the rat.

We evaluated the interaction between neurotensin (NT) and mu-opioid receptors at the locus coeruleus (LC), using fentanyl-induced muscular rigidity as our experimental index. Adult, male Sprague-Dawley rats anesthetized with ketamine (120 mg/kg, i.p., with 24 mg/kg/h i.v. infusion supplements) were used. Intravenous injection of fentanyl (100 micrograms/kg) consistently promoted a significant increase in the electromyographic activity recorded from the sacrococcygeus dorsalis lateralis muscle. This implied muscular rigidity was appreciably and dose-dependently antagonized by prior intracerebroventricular (i.c.v.) application of NT (15, 30 or 60 nmol/5 microliter). Microinjection of the tridecapeptide (300 or 600 pmol/100 nl) into the bilateral LC produced similar results. This suppressive effect of NT on fentanyl-induced muscular rigidity was antagonized by simultaneously administered NT antiserum (1:80), or partially blocked by its antagonist, (D-Trp11)-NT (300 pmol), but not by normal rabbit serum (1:80). These results suggest that NT may interact with the mu-opioid receptors at the LC, resulting in the suppression of fentanyl-induced muscular rigidity in the rat.

Substance P suppresses the activity of alpha 2-adrenoceptors of the nucleus reticularis gigantocellularis involved in cardiovascular regulation in the rat.

We evaluated possible interactions between substance P (SP) and the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata involved in cardiovascular regulation. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. supplements) were used. The circulatory suppressant efficacy of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Bilateral microinjection of SP (300 or 600 pmol) into the NRGC, a medullary site that is critically involved in the cardiovascular depressive actions of guanabenz, significantly diminished the hypotensive and bradycardiac efficacy of the aminoguanidine compound (100 micrograms/kg, i.v.). This implied reduction in alpha 2-adrenoceptor activity in the NRGC by SP was antagonized by its selective receptor antagonist, [D-Pro2,D-Trp7,9]-SP (1200 pmol). Similarly, attenuation by SP of the cardiovascular suppressant effects of guanabenz was also reversed by immunocytochemically verified depletion of dopamine-beta-hydroxylase-immunoreactive nerve terminals in the NRGC, elicited by the selective noradrenergic neurotoxin, DSP4 (50 micrograms). These data suggest that SP may exert an inhibitory action on the alpha 2-adrenoceptors in the NRGC that are involved in central cardiovascular regulation, possibly via a presynaptic modulation on noradrenergic neurotransmission.

Participation of noradrenergic neurotransmission in the suppression by substance P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved in central cardiovascular regulation in the rat.

We applied reverse microdialysis and HPLC analysis to quantify the participation of noradrenergic neurotransmission in the modulation by substance P of alpha 2-adrenoceptors at the nucleus reticularis gigantocellularis involved in cardiovascular regulation, using Sprague-Dawley rats anesthetized with pentobarbital sodium. The efficacy of circulatory suppression of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Continuous infusion of substance P (600 or 1200 pmol/microliters/min) into the nucleus reticularis gigantocellularis through a stereotaxically positioned microdialysis probe (active exchange length: 500 microns, diameter: 220 microns) for 80 min elicited a reduction in the hypotensive and bradycardiac actions of guanabenz (100 micrograms/kg, i.v.). This implied suppression of alpha 2-adrenoceptor activity correlated positively with the time-course of increase in the estimated extracellular concentration of the undecapeptide and norepinephrine in the nucleus reticularis gigantocellularis. Experimentally elevating the concentration of norepinephrine at this reticular nucleus via microinfusion by reverse microdialysis also decreased the efficacy of the cardiovascular suppression of the aminoguanidine compound. These results suggest that substance P may depress the activity of the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis that are involved in central cardiovascular regulation via an increase in the extracellular concentration of norepinephrine at this reticular nucleus.

Characterization and application of microdialysis probes with an active exchange length compatible with small-size brain nuclei in the rat.

We communicated the construction, characterization and application of microdialysis probes with an active exchange length that is suitable for experiments involving small-size nuclei in rat brain. Using substance P (SP) as the test substance, we determined that probes with an active exchange length of 180-200 microns exhibited an in vitro recovery of 14.2 +/- 0.8% and in vivo recovery at the nucleus tractus solitarii (NTS) of 24.9 +/- 1.7% for the undecapeptide, calibrated at an infusion rate of 1 microliter/min. We also demonstrated that microinfusion of SP via these probes into the NTS allowed for a correlation of changes in tissue levels of both SP (exogenous substance) and norepinephrine (endogenous substance) with alterations in baroreceptor reflex responses (physiologic phenomenon).

Prostaglandins may participate in opioidergic and cholinergic control of the diurnal changes of tuberoinfundibular dopaminergic neuronal activity and serum prolactin level in ovariectomized, estrogen-treated rats.

The roles of prostaglandins (PGs) involved in opioidergic, cholinergic, and serotonergic regulation of the diurnal changes of tuberoinfundibular dopaminergic (TIDA) neuronal activities were investigated in ovariectomized, estrogen-treated rats. Treatment with naloxone [10 mg/kg, intraperitoneal (i.p.)], atropine (5 mg/kg, i.p.), or ketanserin (10 mg/kg, i.p.) at either 1200 or 1400 h prevented the afternoon decrease of TIDA neuronal activity and the prolactin (PRL) surge. Intracerebroventricular (i.c.v.) injection of PGE(1) (5 microg/3 microl/rat) at 1500 h significantly reversed the effects of naloxone and atropine, but not that of ketanserin. In ovariectomized, estrogen-primed rats pretreated with indomethacin, i.c.v. injection of either nicotine (10 ng/rat) or fentanyl (10 ng/rat) failed to suppress the TIDA neuronal activity and to stimulate the PRL secretion. These data suggest that PG may be involved in opioidergic and cholinergic control of the diurnal changes of TIDA neuronal activity and the PRL secretion in ovariectomized (OVX) + E(2) rats.

Prostaglandins play an important role in diurnal changes of tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in ovariectomized, estrogen-treated rats.

Intracerebroventricular injection of prostaglandins (PGs) has long been shown to stimulate the secretion of prolactin (PRL). The action of specific PG and the underlying mechanism, however, remain inconclusive. In this study, we evaluated the involvement of PGs in the diurnal changes of the tuberoinfundibular dopaminergic (TIDA) neurons and PRL secretion in ovariectomized (OVX) rats treated with estrogen (E2). Prior treatment of indomethacin (50 mg/kg, subcutaneous) for 24 h significantly prevented the afternoon decrease of TIDA neuronal activity and blocked the PRL surge. Intracerebroventricular injection of PGE(1) (5 microg/3 microl/rat) at 1000 h significantly lowered the activity of TIDA neurons, while similar treatment of PGE2 was without effect. In OVX + E(2) rats pretreated with indomethacin, PGE(1) given at 15, but not 30 or 180 min before decapitation at 1500 h significantly reversed the effects of indomethacin on TIDA neuronal activity, while the blocked PRL surge was not reversed. The PGs also exhibited a stimulatory effect on nigrostriatal dopamine (DA) neurons with PGE2 being the most effective agent. These results indicate that endogenous PGs play a significant role in the control of central DA neurons, especially the diurnal changes of TIDA neuronal activity and PRL secretion in OVX + E2 rats.

The optimal effective concentration of lidocaine to reduce pain on injection of propofol.

STUDY OBJECTIVE: To determine the optimal concentration of lidocaine that reduces pain on injection of a propofol-lidocaine mixture. DESIGN: Prospective, randomized, double-blinded, clinical investigation. SETTING: Medical center, university teaching hospital. PATIENTS: 240 ASA physical status I and II female outpatients, aged 21 to 65 years, undergoing dilation and curettage with propofol for anesthesia induction. INTERVENTIONS: Patients were randomized to one of four groups in double-blinded fashion. In Group A (control), patients were given propofol containing normal saline; in Group B, Group C, and Group D, patients received propofol containing 0.05% lidocaine (Group B), propofol containing 0.1% lidocaine (Group C), and propofol containing 0.2% lidocaine (Group D) for induction. MEASUREMENTS AND MAIN RESULTS: The incidence of pain on injection of propofol was significantly decreased in Group C and Group D (8.3% and 10.0%, respectively) in comparison to the control group (91.7%) (p < 0.001). Although the result in Group B (76.7%) was better than that in the control group, the difference was not statistically significant. No significant difference was seen between Group C and Group D. CONCLUSIONS: The optimal effective concentration of lidocaine, which decreased the incidence of pain caused by propofol injection, was 0.1% in the currently studied population.

Thoracic epidural analgesia with morphine does not prevent postthoracotomy pain syndrome: a survey of 159 patients.

BACKGROUND: This retrospective study sought to determine the incidence of postthoracotomy pain syndrome (PTPS), and whether epidural morphine for the postoperative analgesia could prevent the development of PTPS. METHODS: We reviewed the charts of 372 patients who had undergone thoracotomy. The majority underwent general anesthesia (GA) combined with thoracic epidural analgesia (TEA). Of the 372 patients, only 159 (42%) were available for interview. Patients were divided into two groups based on the duration of pain, i.e., pain group (pain > 3 months, n = 65) and pain-free group (pain < 3 months, n = 94). RESULTS: Both groups were comparable regarding sex, age, weight, height, smoking, alcohol ingestion, education, marital status, duration of surgery, and the number of patients either receiving GA plus TEA or GA alone. About 41% of the patients experienced PTPS that persisted for 21 +/- 12 mon (follow-up: 28 +/- 12 mon). Most pain was mild or moderate and was usually described as being only a discomfort. Only 6.2% suffered severe pain with shooting, aching, burning or numbness. Patients with PTPS suffered more depression and insomnia. The incidence of PTPS was not different in patients who received GA alone or GA plus TEA (39% vs. 42%). CONCLUSIONS: Epidural morphine for postoperative analgesia that continued for 3 days appeared to have no effect in the prevention of PTPS.

Anesthetic management of parturients with Eisenmenger's syndrome--report of two cases.

Pregnancy is badly tolerated in patients with Eisenmenger's syndrome; maternal mortality with coherent fetal morbidity is high. Even with the advancement of both obstetric and anesthetic managements, the maternal mortality still exceeds 25%. Once conception occurs in patients of Eisenmenger's syndrome with severe pulmonary hypertension, interruption of pregnancy is still the best manipulation to be recommended. We report two cases of parturients with Eisenmenger's syndrome, who underwent termination of pregnancy. In this report, the obstetric and anesthetic management of this kind of parturients with Eisenmenger's syndrome has been thoroughly discussed.

A modified method for intubation of a patient with ankylosing spondylitis using intubating laryngeal mask airway (LMA-Fastrach)--a case report.

We present an instance of successful use of an intubating laryngeal mask airway (LMA-Fastrach) and a Cook airway exchanger (CAE) for ventilation and intubation in a patient with severe ankylosing spondilitis (AS) receiving total hip arthroplasty. This measure may serve as an effective alternative for airway management in patients with difficult airway. A 61-year-old male was scheduled for right total hip arthroplasty because of degenerative osteoarthritis. He had been suffering from extensive ankylosing spondylitis, with the cervical spine markedly fixed in anterior flexion. Besides he could not open his mouth widely (35 mm when fully open) also because of ankylosis of jaw. Although we advised an awake fiberoptic tracheal intubation for anesthesia but he refused owing to a previous painful experience. After induction of anesthesia with glycopyrrolate, fentanyl, thiamylal sodium and succinylcholine, we inserted a # 5 Fastrach ILMA for primary airway maintenance. Then through the lumen of the ILMA we introduced the CAE as a guide for endotracheal tube (ETT) intubation. After applying the RAPI-FIT adapter to the CAE, we connected it to the capnography monitor for the confirmation of airway. We finally inserted an endotracheal tube into the trachea using the CAE as a guide. The whole procedure was uneventful and smooth. In sum, the modified Fastrach intubation method may facilitate tracheal intubation in patients with severe ankylosing spondilitis. It may be an alternative way for successful airway management in patients with difficult airway.

Repeated attacks of venous air embolism during craniotomy--a case report.

Venous air embolism (VAE) is not uncommon during craniotomy, but repeated attacks of VAE during a single surgical procedure is rarely seen. We report a successful intraoperative management of repeated attacks of air embolism in a patient who sustained craniotomy for intracranial hemorrhage (ICH) in prone position. A 70-year-old male suffering from hemorrhage in the right cerebellar hemisphere with impending brainstem herniation was scheduled for craniotomy. He had history of hypertension but it was not well controlled with medical treatment. Emergent craniotomy for removal of blood clot resulting from ICH was performed. During the operation, sudden decrease of end-tidal CO2 (EtCO2) level, fall of blood pressure and increase of central venous pressure (CVP) were noted. Since air bubbles were retrieved from CVP catheter venous air embolism was highly suspected. With prompt diagnosis and proper management, we successfully improved the patient's hemodynamic status and he was discharged without any sequelae. Early detection together with aggressive treatment is the only way in the management of intraoperative venous air embolism.

A child of suspected malignant hyperthermia during general anesthesia for dental surgery.

Malignant hyperthermia is clinically an uncommon disorder characterized by acute hypercatabolic reactions in muscles in response to the triggering effects of certain drugs mainly used during anesthesia or to physical or emotional stress. We present a pediatric patient with multiple caries who was suspected to contract malignant hyperthermia while underwent the operative procedure of comprehensive restoration. Sinus tachycardia, hyperthermia, hypercapnia, metabolic acidosis, hyperkalemia and hypercalcemia developed unexpectedly during the operation. Fortunately, the patient survived the episode with early recognition and prompt management.

Fatal pulmonary embolism in a child undergoing extra-ventricular drainage surgery--a case report.

Thromboembolism is rather common in neurological patients and patients with brain tumor, who are bed-ridden or with partial immobile limb. In serious instances morbidity and mortality are inevitable. We present a case report on a fatal pulmonary embolism in a 2-year-old girl who underwent extra-ventricular drainage procedure under general anesthesia for occipital subdural effusion, a sequela of the former surgery undertaken to remove the choroid plexus papilloma 13 days ago. Sudden cardiac arrest occurred during induction of anesthesia and she finally succumbed in spite of vigorous cardiopulmonary resuscitation. Transthoracic and transesophageal echocardiography performed in the course of resuscitation disclosed thrombi of various sizes scattering in right atrium, the right ventricle, main pulmonary trunk, and the left pulmonary artery. The cause of death was thought to be severe obstruction of right ventricular outflow tract by large thrombi. The etiological factors which possibly led to the thrombosis were discussed, and the methods of diagnosis and treatment were also explored.

Pre-anesthetic oral clonidine is effective to prevent post-spinal shivering.

BACKGROUND: Shivering is a common event during spinal anesthesia. Customarily we just treat it rather than prevent it. This study was designed to evaluate the efficacy of oral clonidine as a premedication to prevent post-spinal shivering. METHODS: One hundred males of ASA physical status I-III, aged above 40, scheduled for elective urological surgery under spinal anesthesia, were included in this study. All participants were randomly divided into the clonidine and control groups. They received either oral clonidine 150 micrograms (n = 48) or placebo (n = 52) 90 min before spinal anesthesia in a double-blind fashion. Spinal blockade was induced with heavy bupivacaine to a dermatomal level near T10. The shivering was graded as: none, no perceptible tension of muscles observed; mild, slight muscle tonus (masseter muscle); moderate, real shivering (proximal muscles); and severe, generalized shivering (whole body). The tympanic membrane temperature was recorded 30 min after spinal anesthesia. Data were expressed as mean +/- standard deviation. Chi-square and Student's t-test were used. A p value less than 0.05 was considered statistically significant. RESULTS: The incidence of post-spinal shivering, which was graded as none, mild, moderate, and severe, showed statistically significant differences (p < 0.05) between clonidine 150 micrograms and placebo (83% vs. 42%, 10% vs. 6%, 10% vs. 19%, 0% vs. 33%, respectively) during the 30 min immediately after spinal anesthesia. The respective mean tympanic temperature in oral clonidine and placebo groups showed no difference (clonidine vs. control = 35.9 +/- 0.8 degrees C vs. 35.9 +/- 0.7 degrees C). CONCLUSIONS: Pre-anesthetic medication with oral clonidine 150 micrograms is effective to prevent post-spinal shivering in patients undergoing elective urological surgery.