An improved system for quantifying AgNOR and PCNA in canine tumors.

BACKGROUND: Quantifying silver stained nucleolar organizer regions (AgNORs) and proliferation cell nuclear antigens (PCNA) are useful techniques to measure proliferative activity of tumor cells; however, the nonspecific deposition of stains and overlappings of AgNOR and PCNA counts between grades of tumors hamper their applications. MATERIALS AND METHODS: Fifty-two surgical specimens from dogs, including mast cell tumors, perianal gland tumors and hyperplasias, fibromas, fibrosarcomas, and normal tissues were studied. The 3 microns dewaxed sections of formalin-fixed tissues were stained to detect AgNORs by a modified inverted incubation technique in a newly developed silver staining device. Data were collected and analyzed using a high-resolution digital microscope camera and image analysis software. Sequential sections were also stained for PCNA using an immunohistochemical method. RESULTS: The improved system for quantifying AgNOR provided more accurate and non-overlapping mean AgNOR counts, which enable us to distinguish benign states from malignant changes. The mean AgNOR cut-off points that discriminated grade II or III mast cell tumors from grade I, perianal gland carcinomas from adenomas (or hyperplasia), fibrosarcomas from non-fibrosarcoma tissues, were 6.0, 14.1, 9.4, and 8.8 respectively. The mean AgNOR areas, relative AgNOR areas, and PCNA positive rates of some malignant and non-malignant tissues (benign tumor and normal tissues) were significantly different (P < 0.05). CONCLUSIONS: This improved system is a sensitive and rather precise method for quantifying the AgNOR and PCNA. It provides a valuable objective measurement for differentiating benign and malignant tumors.

Clinical experience in anesthetic management for children with mucopolysaccharidoses: Report of ten cases.

The mucopolysaccharidoses (MPS) are hereditary disorders. Children with these disorders have multisystem disease and present significant challenges for the anesthesiologist. The establishment and maintenance of an adequate airway represents the most commonly encountered anesthesia-related problem in these patients. We report ten children with MPS who required surgical intervention. One patient died and the others had a good outcome. In this report, we share our experience and discuss the anesthetic risks and management of MPS patients.

Effects on the bispectral index during elective caesarean section: a comparison of propofol and isoflurane.

BACKGROUND: Awareness during general anesthesia has been a particular problem during caesarean section. About 7 percent of patients undergoing elective caesarean section have reported dreaming or recall of voices during the procedure. The bispectral index (BIS), a value derived from the electroencephalogram (EEG), has been shown to be useful in monitoring the depth of anesthesia. Supplementation of propofol or isoflurane for maintenance of anesthesia has been shown to effectively reduce the incidence of awareness. However, the effects of propofol or isoflurane on the BIS index have not been fully investigated. We therefore designed this study to compare the effects of isoflurane or propofol supplementation on the BIS index in 24 healthy parturients undergoing elective caesarean section. METHODS: All patients had induction of anesthesia and orotracheal intubation in rapid sequence made possible by 1 MAC isoflurane with 50% N2O-50% O2 as conveyer and atracurium. After delivery, patients were randomly assigned to either of two groups (isoflurane or propofol). Patients in the Isoflurane group (n = 12) received 0.5 MAC isoflurane in 67% N2O-33% O2 and fentanyl + droperidol. Patients in the propofol group (n = 12) received propofol (8 mg/kg/h) infusion combined with 67% N2O-33% O2 and fentanyl + droperidol. RESULTS: There was no difference between the two groups in total operation time, maternal blood loss, fetal Apgar scores. No differences between the two groups in heart rate, blood pressure or BIS index values were found throughout the surgery. No patient from either group reported recall of the operative procedure. However, 25% of patients (3 of 12) in the isoflurane group had poor uterine contraction, suggestive of doubtful appropriateness of the use of isoflurane for maintenance of anesthesia in delivery. CONCLUSIONS: We therefore concluded that supplementation of isoflurane or propofol for maintenance of anesthesia can satisfactorily decrease the BIS index and minimize the incidence of awareness in patients undergoing caesarean section under general anesthesia. The BIS index is a reliable monitor of the hypnotic component of anesthesia.

Comparison of inhalation induction with 2%, 4%, 6%, and 8% sevoflurane in nitrous oxide for pediatric patients.

BACKGROUND: Sevoflurane is almost the idealest volatile anesthetic agent regarding inhalation induction of general anesthesia. Previous studies have established a role of sevoflurane in high concentration primed in the circuit for inhalation induction in pediatric patients. However, which concentration of sevoflurane is suitable has not yet been reported. This study was designed to compare the efficiency of different concentration of sevoflurane i.e. 2%, 4%, 6%, and 8% and with N2O in 50% oxygen for induction of anesthesia in pediatric patients and at the same time to evaluate the tolerance of patients. METHODS: One hundred and twenty children who were 3 to 10 years old, of ASA class I, were randomly assigned to receive either 2%, 4%, 6%, and 8% sevoflurane and N2O in 50% O2 for induction of anesthesia. The time to loss of eyelash reflex, responses of airway reflex, involuntary movement, and hemodynamic responses were recorded. RESULTS: Ninety-nine children completed the study. The times to loss of eyelash reflex with 2% in sequence to 8% sevoflurane were 114 +/- 21 s, 87 +/- 11 s, 75 +/- 6 s, and 48 +/- 8 s respectively. Incidence of airway reflex response including coughing, laryngospasm, and breath holding was the highest in the 8% group (P < 0.05). Inhalation induction with sevoflurane significantly decreased systolic as well as diastolic blood pressure compared with baseline blood pressure in all the four groups. The extent of decrease of blood pressure was within 20% range of baseline blood pressure in all groups. Significant increase of heart rate was only observed in the 4% and 6% groups. CONCLUSIONS: Sevoflurane 6% for inhalation induction apparently caused low incidence of adverse effects and hastened induction. We suggest that 6% sevoflurene is a concentration more practical for inhalation induction in pediatric patients.

Prevention of PONV with dexamethasone in female patients undergoing desflurane anesthesia for thyroidectomy.

BACKGROUND: Desflurane is associated with a higher incidence of 24-h postoperative nausea and vomiting (PONV) as compared with sevoflurane or isoflurane. Dexamethasone 5 mg i.v. is suggested to be the minimum effective dose for prophylaxis of PONV in women undergoing thyroidectomy with isoflurane anesthesia. The objective of this study was to investigate whether a 5 mg dose of dexamethasone could be enough for, or a larger dose at 8 mg, could be more capable of preventing PONV in women undergoing desflurane anesthesia for thyroidectomy. METHODS: One hundred and thirty five patients were assigned to receive one of three treatment regimens prior to induction i.e., dexamethasone 8 mg i.v. (Group D8), dexamethesone 5 mg i.v. (Group D5) or saline (Group S). RESULTS: It was demonstrated that the prophylactic administration of either dexamethasone 8 mg or 5 mg significantly reduced the overall incidence of PONV in patients undergoing thyroidectomy with desflurane anesthesia (P < 0.001, Group D8 vs. Group S; Group D5 vs. Group S). However, patients who received dexamethasone 8 mg showed a higher incidence of complete responses (no vomiting or need of rescue antiemetic medication for a 24-h postoperative period) in comparison with those receiving dexamethasone 5 mg (86% vs. 67%; P < 0.01). CONCLUSIONS: The results of this study showed that in PONV prophylaxis, in female patients undergoing desflurane anesthesia for thyroidectomy, the effect of dexamethasone 8 mg was superior to that of dexamethasone 5 mg.

Premedication with low-dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurane anesthesia.

BACKGROUND: Sevoflurane is a volatile anesthetic agent with low pungency, non-irritating odor, and low blood/gas partition coefficient that makes it an attractive alternative to halothane. However, a high incidence of emergence agitation (EA) has been reported in pediatric patients after sevoflurane anesthesia. The underlying mechanism of sevoflurane-induced EA remains unclear. Rapid recovery of consciousness (emergence) from sevoflurane anesthesia has been proposed as one possible mechanism. We, therefore, hypothesized that sedatives such as midazolam may counteract sevoflurane's rapid emergence and thus reduce the incidence and the severity of sevoflurane-induced EA. METHODS: A prospective, controlled, single-blinded study was carried out in 88 ASA class I or II pediatric patients scheduled for elective outpatient surgery. Patients were assigned to receive either midazolam (oral midazolam, 0.2 mg/kg as anesthetic premedication) or saline (oral normal saline as premedication) before the conduct of anesthesia. When separation from parents was due its process was watched and evaluated. Induction of anesthesia and maintenance of anesthesia were uniform in both groups. Induction of anesthesia was made possible with 8% sevoflurane and N2O in 50% O2. Intubation was performed straight without the aid of muscle relaxant and the ventilator was set to maintain normocapnia. Anesthesia was maintained with 3% sevoflurane and N2O in 50% O2 until the surgery was over. All matters of relevant time periods were recorded (induction, surgical procedure, extubation and transportation). In the post-anesthesia care unit (PACU), adverse events, the incidence and the severity of EA, analgesic requirement, duration of PACU stay, and parental as well as PACU nurses' satisfaction were evaluated. RESULTS: A significant lower incidence and less severity of EA were noted in patients premedicated with midazolam. Less postoperaive analgesia was required in patients who had received midazolam. Although midazolam-premedicated patients remained sedated after sevoflurane anesthesia, the duration of the PACU stay was not significantly different from that of saline-treated patients. Both parents and PACU nurses were more satisfied with midazolam as premedication. No solid evidence showed that there was close correlation between the process of separation from parents and the occurrence of EA. CONCLUSIONS: Premedication with oral midazolam is safe, convenient and effective in decreasing the occurrence of sevoflurane-induced EA. It does not delay discharge from PACU and is suitable for outpatient surgery.

Pulmonary edema induced by upper airway obstruction--report of 3 cases.

Pulmonary edema is a well-recognized complication of upper airway obstruction, and has been reported sporadically both in children and adults since 1977. Although the pathogenesis of pulmonary edema associated with upper airway obstruction is multifactorial, attention is primarily focused on excessive negative intrapleural and transpulmonary pressure produced by forceful inspiration against a closed glottis that results in transudation of fluid from the pulmonary capillary into the interstitial and alveolar spaces. We report 3 cases of pulmonary edema induced by upper airway obstruction after extubation following general anesthesia.

[A proper size of endotracheal tube for infant and young child--a retrospective study in Mackay Memorial Hospital].

BACKGROUND: There are more than 2000 pediatric patients receiving surgery in Mackay Memorial Hospital each year. Most of these surgery were performed under general anesthesia with endotracheal tube; therefore choosing an appropriate size of endotracheal tube becomes an important issue in our daily practice. METHODS: Our principle is to choose an uncuffed Mallinckrodt endotracheal tube with a proper internal diameter (ID), ranging from 2.5 mm to 6.5 mm, which could be suitably and gently inserted into the trachea under full muscle relaxation. The tube would then be immediately removed and replaced with a smaller one if facing obvious resistance during intubation. After intubation, a leak test was applied to ascertain that there was no excessive gas leakage. We reviewed all anesthetic records of elective pediatric surgery in the recent 6 years, and the patients whose age above 8.5 years old and body weight (Wt) above 30 kg were excluded from this study. Using age (6476 cases) and Wt (6406 cases) as our parameters, we analyzed these data according to the distribution of each size of uncuffed endotracheal tube (UCETT) in different age and Wt intervals and compared them with the recommended Western reports. RESULTS: Our results revealed that (1) the UCETT size increases as age or Wt increases; (2) considerable spread of UCETT sizes for different age and Wt intervals and basically represent as normal distribution; (3) for the case of even age equal or above 2 years old (up to 8 years old), the ID of the most frequently used UCETT can be memorized as (18 + age in years) divided by 4 or the outer circumference (OC) of the Mallinckrodt UCETT (in French unit, Fr) = 19 + age in years; and (4) Wt as a parameter for tube size selection was as powerful as age (94.76% vs. 94.65%). CONCLUSIONS: From our results, we concluded that "whatever method of predicting tube size is used, tracheal tubes 0.5 mm larger and smaller should be available at the time of intubation so that the proper size can be chosen when the glottis is visualized."

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report.

Phrenic nerve paralysis is a common complication in interscalene brachial plexus block. This complication is often ignored by most anesthesiologists because no clinical symptoms occur in patients who have no underlying lung disease. We present a case of an obese male suffering from dyspnea due to phrenic nerve block after interscalene brachial plexus block. The decreased respiratory reserve and direct compressing effect of the abdominal organs on the diaphragm in the supine position are thought to be the risk factors in this obese patient. Also discussed are the incidence, diagnostic methods, clinical presentation and treatments of phrenic nerve paralysis during interscalene brachial plexus block.

Comparison of the cuffed oropharyngeal airway and laryngeal mask airway in spontaneous breathing anesthesia.

BACKGROUND: The cuffed oropharyngeal airway (COPA) is a modified Guedel airway with a cuff at its distal end and a standard 15 mm connector at its proximal end. This study was performed to determine if the COPA would offer any advantage over the laryngeal mask airway (LMA). METHODS: Eighty ASA class I to II adult patients scheduled for short elective procedures (less than 1 h) were randomly allocated into two groups. All patients were given atropine 0.01 mg/kg, fentanyl 2 micrograms/kg and propofol 2 mg/kg intravenously for induction of anesthesia. The COPA or LMA was inserted following the loss of eyelash reflex. If the jaw was not relaxed enough for insertion of a COPA or LMA, succinylcholine 1 mg/kg was given to facilitate the insertion. When correctly positioned, the cuff was immediately inflated with an appropriate volume. Gentle positive pressure ventilation was applied before spontaneous breathing resumed. Capnography was used to assess the patency of the airway. Anesthesia was maintained with isoflurane-N2O-O2 until the end of surgery. The success rate, vital signs, and adverse events were evaluated and compared. RESULTS: The success rate in the LMA group (95%) was higher than the COPA group (85%). The increase in circulatory response after the LMA insertion was greater than that after the COPA insertion (P < 0.05). Nine patients (22.5%) in the LMA group needed succinylcholine to facilitate insertion compared with only two patients (5%) in the COPA group. Additional manipulation was frequently (57.5%) needed after inserting the COPA to maintain the patency of the airways, but none needed so in the LMA group. Two patients had laryngospasms upon removal of the LMA, but none had laryngospasm in the COPA group. The incidence of sore throat in the LMA group was higher than in the COPA group (18% vs. 10%). CONCLUSIONS: We demonstrated that the COPA could be easily inserted without the need of muscle relaxants in most patients. But the COPA needed airway intervention to provide an effective airway in most patients. Compared with the LMA, the COPA caused less stimulation than the LMA.

The use of intranasal nitroglycerin to prevent pressor responses during intubation in general anesthesia--a comparison of various doses.

BACKGROUND: Intranasal nitroglycerin (NTG) was first reported to successfully prevent an increase in arterial blood pressure following laryngoscopy and tracheal intubation by Hill et al. Various different effective dosages of NTG have been reported. Grover et al. indicated 0.75 mg of intranasal NTG to be the most suitable dose. However, no definite conclusion has yet been made. This study was designed to compare the efficacy of four different dosages of intranasal NTG (0.3, 0.5, 0.75, and 1.0 mg) in preventing pressor responses to laryngoscopy and tracheal intubation during the induction of general anesthesia. METHODS: One hundred patients (ASA I or II) scheduled for elective surgery were included. These study subjects were divided into five groups and randomly assigned to four different dosages of intranasal NTG and a placebo. Each group consisted of 20 patients. The NTG solution was administered 1 min before the injection of thiopental. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were recorded before the induction of anesthesia (T1), before laryngoscopy (T2), and at 0, 3, and 5 min after tracheal intubation (T3, T4, and T5 respectively). RESULTS: In patients who received a placebo (control group), there were significant increases in SAP, MAP, HR and rate-pressure-product (RPP) associated with tracheal intubation. Tachycardia was noted in all experimental groups. The increases in MAP associated with tracheal intubation were significantly less in patients who received NTG of 0.5 mg or more but not 0.3 mg. Although 0.5 mg of NTG did attenuate the increases in SAP after tracheal intubation, the increases in SAP of the other three experimental groups were no less than that of the control group. Rate-pressure-product (RPP) values of the experimental groups were noted to be equal to or higher than those of the control group during the period of study. Contrary to the results of the study conducted by Grover et al., 0.75 mg of NTG did not attenuate the pressor responses. CONCLUSIONS: Intranasal NTG does not attenuate the pressor responses to laryngoscopy and tracheal intubation.

Children with mucopolysaccharidoses--three cases report.

The mucopolysaccharidoses (MPS) are a group of inherited disorders of metabolism, with widespread, progressive involvement and derangement of many organs and tissues. Because of their disabling nature, frequent surgical intervention for the abnormality entailed is common, and is associated with a high degree of anesthetic risks perioperatively. One of the major hazards which we find clinically is airway difficulty. Multiple factors are present in the mucopolysaccharidoses to make airway management and trachael intubation potentially hazardous. Aside from generalized infiltration and thickening of the soft tissues, the oropharynx may be obstructed by a large tongue with tonsillar hypertrophy. Also, the friable mucosa covering the nasal and oral pharynx renders these structures easily to bleed and edematous. The neck is typically short and immobile, and the cervical spine and tempromandibular joint may have a limited range of movement. From our experience, we have learned not to overlook the propensity of airway difficulty. The uniqueness of their anatomy and extremely sensitive airway often result in failed intubation and bronchospasm even after successful intubation. Recently, in Mackay Memorial Hospital we have encountered in series three pediatric cases with mucopolysaccharidoses (one Hurler and two Hunter syndromes). In this report we would like to share our experiences and to discuss the anesthetic risks and management of the MPS patients.

Postoperative myocardial infarction in a patient with perioperative ST-depression--a case report.

Often we ignore electrocardiogram (EKG) evidence of ischemia and no adverse events occur. However, once in a while these ischemic episodes will turn into a full-blown myocardial infarction. Therefore, studying perioperative events which tilt the balance over to postoperative myocardial infarction (PMI) can enlighten our knowledge in postoperative myocardial infarction (MI) prevention. We present a case of ST depression in perioperative EKG evolving into postoperative MI. In this paper we attempt to explore various possibilities which could have altered this patient from her ischemic state into an infracted event.

[A study of commonly used substitutes for Chinese drug cortex Eucommiae(Duzhong)].

We have found that 48 species belonging to 10 families and 17 genera are being used as ethnic substitutes for Cortex Eucommiae (Duzhong). A key to all the species has been made to identify them and to distinguish them from Eucommia ulmoides.

Renal transcription of high-affinity type-2 cationic amino acid transporter is up-regulated in LPS-stimulated rodents.

OBJECTIVE: Sepsis stimulates renal nitric oxide (NO) biosynthesis through up-regulation of inducible NO synthase (iNOS) expression. Type-2 cationic amino acid transporter (CAT-2) mediation of trans-membrane L-arginine (L-Arg) transportation has been identified as one of the crucial regulatory mechanisms involved in the formation of NO by iNOS. We had previously shown that CAT-2B, a high-affinity alternative-spliced transcript of the CAT-2, is involved in induced NO biosynthesis by iNOS (Nitric Oxide, 2002). In this present study, we sought to assess the effects of sepsis on the expression of CAT-2B in lipopolysaccharide (LPS)-stimulated rat kidney. METHODS: Forty rats were randomized to either a normal saline (N/S)-treated group or a LPS-treated group. Renal NO production was determined using chemiluminescence. Semi-quantitative RT-PCR was used to determine the mRNA concentrations of iNOS and L-Arg transporters (CAT-1, CAT-2 and CAT-2B) in kidney. RESULTS: Lipopolysaccharide-coinduced iNOS, CAT-2 and CAT-2B mRNA expression in kidney and caused renal NO overproduction. A significant linear regression relationship was defined between renal NO concentrations and iNOS, CAT-2 and CAT-2B, respectively. On the contrary, CAT-1 expression was not affected by LPS-stimulation. CONCLUSIONS: We provide the first evidence to illustrate that sepsis/septic shock induces the transcription of high-affinity CAT-2B in renal tissues. Transcription of iNOS, CAT-2 and CAT-2B correlates well with renal NO biosynthesis. Regulation of L-Arg uptake by modulating the expression regulation of induced CAT-2 and CAT-2B might be a potential target for therapies against renal pathologic conditions related to NO overproduction.

In vitro diffusion of lidocaine across endotracheal tube cuffs.

PURPOSE: Lidocaine diffuses across endotracheal tube cuffs, which may serve as a reservoir for local anesthetic to assist in the prevention of ETT-induced cough while emerging from general anesthesia. However, the rate of diffusion is slow. Two techniques, alkalization and warming, may increase the proportion of uncharged drug available for diffusion. The purpose of this study is to determine the effectiveness of warming alkalization or warming with alkalization on diffusion. METHODS: Four preparations of lidocaine 4% were studied. Group (Gr) L-lidocaine (24 degrees C), Gr WL--warmed lidocaine (38 degrees C), Gr AL--alkalized lidocaine (24 degrees C), Gr WAL--warmed, alkalized lidocaine (38 degrees C). Twenty-four Mallinckrodt 8.0 ID (Mallinckrodt Critical Care Division of Mallinckrodt, Inc., Glens Falls, New York) endotracheal tube cuffs were filled with 6 ml of one of the four preparations. They were then placed in a 20 ml water bath at 38 degrees C and samples were drawn from the water bath at intervals for up to 360 min. The lidocaine concentration in each sample was determined by gas chromatography. RESULTS: The highest lidocaine concentration was reached in Gr WAL (410.98 +/- 8.53 micrograms.ml-1) after 300 min and then decreased to 376.18 +/- 4.59 micrograms.ml-1 after 360 min. In Gr AL the highest concentration (235.05 +/- 2.99 micrograms.ml-1) was reached after 360 min. Lidocaine concentrations in Gr L and WL after 360 min were 3.19 +/- 1.16 micrograms.ml-1 and 4.32 +/- 2.02 micrograms.ml-1 respectively. CONCLUSION: Alkalization with or without warming, but not warming alone, promotes lidocaine diffusion from endotracheal tube cuff.

NF-kappaB involvement in the induction of high affinity CAT-2 in lipopolysaccharide-stimulated rat lungs.

BACKGROUND: Endotoxemia stimulates nitric oxide (NO) biosynthesis through induction of inducible NO synthase (iNOS). Cellular uptake of L-arginine, the sole substrate for iNOS, is an important mechanism regulating NO biosynthesis by iNOS. The isozymes of type-2 cationic amino acid transporters, including CAT-2, CAT-2A, and CAT-2B, constitute the most important pathways responsible for trans-membrane L-arginine transportation. Therefore, regulation of CAT-2 isozymes expression may constitute one of the downstream regulatory pathways that control iNOS activity. We investigated the time course of enzyme induction and the role of nuclear factor-kappaB (NF-kappaB) in CAT-2 isozymes expression in lipopolysaccharide-(LPS) treated rat lungs. METHODS: Adult male Sprague-Dawley rats were randomly given intravenous injections of normal saline (N/S), LPS, LPS plus NF-kappaB inhibitor pre-treatment (PDTC, dexamethasone, or salicylate), or an NF-kappaB inhibitor alone. The rats were sacrificed at different times after injection and enzyme expression and lung injury were examined. Pulmonary and systemic NO production were also measured. RESULTS: LPS co-induced iNOS, CAT-2, and CAT-2B but not CAT-2A expression in the lungs. Furthermore, NF-kappaB actively participated in LPS-induction of iNOS, CAT-2, and CAT-2B. LPS induced pulmonary and systemic NO overproduction and resulted in lung injuries. Attenuation of LPS-induced iNOS, CAT-2, and CAT-2B induction significantly inhibited NO biosynthesis and lessened lung injury. CONCLUSION: NF-kappaB actively participates in the induction of CAT-2 and CAT-2B in intact animals. Our data further support the idea that CAT-2 and CAT-2B are crucial in regulating iNOS activity.

[Does flumazenil antagonize the anesthetic effect of ketamine, etomidate or thiopental?].

The effect of flumazenil, a benzodiazepine antagonist, was assessed in a random, double-blind clinical study in which each of the four groups of surgical outpatients comprising 20 in each was given either ketamine 100 mg (K), etomidate 20 mg (E), thiopental 300 mg (T) or flunitrazepam 4 mg (F) for induction of anesthesia. On emergence, patients in each group were randomly given 2cc of either 2 coded solutions, one of which contained 0.2 mg flumazenil and the other of which was normal saline. Following injection of coded solution, all patients were assessed at 0, 5, 15, 30, 60 and 120 min for wakefulness. All 10 patients of group F who received flumazenil were alert and able to recall at 5 min, whereas in group T this was noted from 15 to 30 min. Patients of group E and K responded alike in a manner as of those who received normal saline placebo with onset of wakefulness at 30 and 60 min respectively. These results confirm that flumazenil antagonizes flunitrazepam (within 5 min) and also indicate that the antagonizing effect occurs 30 min following injection for thiopental, suggestive of some cross-reactivity between these two drugs.