Beyond Ether and Chloroform-A Major Breakthrough With Halothane.

BACKGROUND: The use of equipment powered by electricity in the operating room increased the risk of fires in the presence of flammable agents such as ether and cyclopropane. Chloroform was associated with cardiac arrhythmias and liver damage. The introduction of halothane in the late 1950s was heralded as a solution to many problems facing the specialty of anesthesia. We explore whether the manufacturer promptly reported halothane's adverse effects to regulatory agencies and practitioners. SOURCES: We consulted documents submitted by Ayerst Laboratories to federal authorities through the Freedom of Information Act, promotional advertisements, package inserts, published articles, and textbooks. RESULTS: Two major complications associated with the use of halothane, cardiac arrhythmias and the risk of hepatotoxicity, were disclosed by the manufacturer when the drug was first introduced to the US market. Reports appeared timely and complete; there was no apparent attempt to conceal or otherwise downplay these risks. CONCLUSION: The process of drug discovery and approval for clinical use has always been a lengthy, complex, and extremely expensive undertaking, with only a small minority of compounds receiving approval. The risk of adverse effects or drug interaction directly impacts commercial viability. In the case of halothane, the manufacturer disclosed major adverse effects, and the drug enjoyed decades of popularity until it was replaced by agents with a better drug profile.

[Experience with sevofluorane and halothane used during general anesthesia in children].

The investigators made a prospective analysis of the specific features of anesthesias with sevoflurane and halothane in 70 children aged 1 to 11 years with systemic surgical diseases and assessed their physical status as ASA Class I. The anesthetics sevoflurane, 3.1 +/- 0.7 MAC, and halothane, 2.4 +/- 0.3 MAC, were used to induce anesthesia. Sevoflurane, 1.6 +/- 0.6 MAC, and halothane, 1.5 +/- 0.4 MAC, were employed to maintain anesthesia. In children, sevoflurane anesthesia induction and emergence occurred by 49% more rapidly (p < 0.001) than halothane use (the time of induction 2.9 +/- 0.7 min for sevoflurane versus 5.7 +/- 0.5 min for halothane; that of consciousness recovery 3.6 +/- 0.7 min versus 7.0 +/- 1.2 min). After halothane anesthesia anesthesia, there was a significant reduction in mean blood pressure (BP) by 24.5% as compared with the baseline values (p < 0.001). Sevoflurane use demonstrated a significantly less reduction in systolic BP--by 10.2% of the baseline value (p < 0.001). In both groups after induction, there was a decrease in tidal volume, but minute volume was insignificantly lower due to higher respiration rate. The level of blood oxygenation was stable (SpO2 97-99%) in both groups during all observational stages. No severe complications were recorded in both groups during anesthesia. However, mild or moderate complications were twice fewer in the sevoflurane group.

[Electroencephalographic monitoring during sevofluorane and halothane anesthesia in children].

Twenty-two children aged 5 to 15 years were examined. Ten children underwent fluorothane; 12 received a combination of sevofluorane and isofluorane. EEG was continuously recorded by a 9-channel computer-assisted encephalograph via bilateral electrode placement and BIS values were simultaneously measured. In the fluorothane group, EEG displayed a gradual reduction in basic rhythm, an increase in slow activity with the rhythm being recovered on emergence. The BIS index changed from 95-98 to 40-45 with a spike up to 78-84 on emergence. In the sevofluorane group, EEG recorded a pointed alpha rhythm, increased amplitude, and rhythm synchronization. The isofluorane anesthesia stage changed EEC patterns towards a reduction in cortical rhythm with slow fluctuations. The BIS value changed from 96-99 to 19-25 with 35-40 on anesthesia maintenance and up to 82-87 on emergence. The BIS data agree with EEG readings at all anesthesia stages.

ECoG studies of valproate, carbamazepine and halothane in frontal-lobe epilepsy induced by head injury in the rat.

The use of electrocorticography (ECoG) with etiologically realistic epilepsy models promises to facilitate the discovery of better anti-epileptic drugs (AEDs). However, this novel approach is labor intensive, and must be optimized. To this end, we employed rostral parasagittal fluid percussion injury (rpFPI) in the adolescent rat, which closely replicates human contusive closed head injury and results in posttraumatic epilepsy (PTE). We systematically examined variables affecting the power to detect anti-epileptic effects by ECoG and used a non-parametric bootstrap strategy to test several different statistics, study designs, statistical tests, and impact of non-responders. We found that logarithmically transformed data acquired in repeated-measures experiments provided the greatest statistical power to detect decreases in seizure frequencies of preclinical interest with just 8 subjects and with up to approximately 40% non-responders. We then used this optimized design to study the anti-epileptic effects of acute exposure to halothane, and chronic (1 week) exposures to carbamazepine (CBZ) and valproate (VPA) 1 month post-injury. While CBZ was ineffective in all animals, VPA induced, during treatment, a progressive decrease in seizure frequency in animals primarily suffering from non-spreading neocortical seizures, but was ineffective in animals with a high frequency of spreading seizures. Halothane powerfully blocked all seizure activity. The data show that rpFPI and chronic ECoG can conveniently be employed for the evaluation of AEDs, suggest that VPA may be more effective than CBZ to treat some forms of PTE, and support the theory that pharmacoresistance may depend on the severity of epilepsy. The data also demonstrate the utility of chronic exposures to experimental drugs in preclinical studies and highlight the need for greater attention to etiology in clinical studies of AEDs.

Does the choice of the halogenated anesthetic influence renal function during hemorrhagic shock and resuscitation?

INTRODUCTION: Halogenated anesthetics can cause changes in the variables that modify the cardiac output necessary to maintain renal hemodynamic during hemorrhagic shock and resuscitation. However, halogenated anesthetics seem to protect against renal ischemia-reperfusion injury. In a model of pressure-guided hemorrhagic shock in dogs, we studied the comparative effects of three halogenated anesthetics-halothane, sevoflurane, and isoflurane-at equipotent concentrations on renal responses after resuscitation. METHODS: Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane, sevoflurane, or isoflurane. The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40-50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamic variables were measured at baseline, after 45 min of hemorrhage, and 15 and 60 min after resuscitation. Renal variables were measured at baseline and 15 and 60 min after resuscitation. RESULTS: Hemorrhage induced reductions of mean arterial pressure, filling pressures, and cardiac index (p < 0.05), without significant differences among groups (p > 0.05). After 60 min of shed blood replacement, all groups restored hemodynamic and renal variables to the prehemorrhage levels (p > 0.05), without significant differences among groups (p > 0.05), with the exception of sodium fractional excretion, the values for which were significantly higher in isoflurane group, in relation to the other groups after 15 min of re-transfusion (p < 0.05), and renal vascular resistance, the values for which remain lower than baseline in halothane group (p < 0.05). CONCLUSIONS: We conclude that no difference could be detected between choosing equipotent doses of halothane, sevoflurane, or isoflurane in relation to renal variables in dogs submitted to pressure-adjusted hemorrhagic shock and resuscitation.

Mirando hacia atrás. Los últimos diez años de anestesia-reanimación y tratamiento del dolor / No disponible

Se revisan los avances más importantes en los últimos diez años respecto a los fármacos anestésicos, la tecnología incorporada a la práctica clínica y la organización de los servicios de anestesia-reanimación y tratamiento del dolor. Las nuevas formulaciones, las interacciones, el tratamiento de la sepsis, las distintas generaciones son algunos de los aspectos revisados (AU)

This review highlights some recent advances in the last ten years in anaesthesia, intensive care and pain treatment. Pharmacology, technology and organization of our departments are the aims of this review. New drugs, new formulations, the study of anaesthetic interactions, the treatment of sepsis, and the different generations in the departments of anaesthesia are review (AU)

The performance of Bispectral Index in children during equi-MAC halothane vs. sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: The reliability of the Bispectral Index for evaluating and monitoring the depth of general anaesthesia in children is not as great as for that in adults. Therefore we analysed Bispectral Index performance in children by comparing changes in Bispectral Index values during a standardized and equipotent anaesthetic regimen using either halothane or sevoflurane for the induction and maintenance of general anaesthesia. Special interest was focussed on excitation during induction, and whether it was associated with simultaneous changes in Bispectral Index scores. METHODS: Twenty children (3-15 yr, ASA I-II) scheduled for general surgery were randomly allocated to either halothane (10 patients) or sevoflurane group (10 patients). Anaesthesia was induced by 3% halothane or 7% sevoflurane, either agent administered with 50% N2O in oxygen for 5 min, the period from the beginning of induction until intubation. Thereafter, anaesthesia was maintained by the respective volatile agent at 1 MAC (minimum alveolar concentration; in addition to 70% N2O in oxygen) and supplemented with remifentanil infusion adjusted to maintain the heart rate and mean arterial pressure to within 20% of the baseline values. Excitation at induction was defined as involuntary muscular movements. RESULTS: Sevoflurane induction produced a more rapid depression in Bispectral Index than halothane, the mean difference being greatest (47 Bispectral Index score) at 105 s. Excitation occurred in three patients during sevoflurane induction, which coincided with increases in Bispectral Index values in two of the three patients. During the maintenance phase at 1 MAC, the Bispectral Index (mean +/- SD) was 57+/-7 for halothane and 47+/-9 for sevoflurane (P < 0.05). The remifentanil doses did not differ between both groups. CONCLUSION: In children, halothane anaesthesia was associated with higher Bispectral Index values than sevoflurane when administered at 1 MAC. Large individual variation in Bispectral Index occurred within both groups. Due to these limitations, one should be cautious when interpreting paediatric Bispectral Index data.

Reduced incidence of laryngospasm with remifentanil-midazolam anaesthesia compared to halothane-fentanyl.

OBJECTIVE: To compare the incidence of laryngospasm by using halothane-fentanyl anaesthesia and midazolam-remifentanil anaesthesia in paediatric patients undergoing eye surgery. METHODS: We enrolled 120 ASA physical status I children aged 7-12 years scheduled for eye surgery from March 2004 to February 2006 in this prospective clinical trial study. Children suffering from any medical condition that could affect airway reflexes such as active upper respiratory infection, symptomatic asthma, obesity, patients with predicted difficulty in tracheal intubation were not included in the study. Patients with prolonged or difficult intubation or those who received another drug before extubation were excluded from the study. Using a random numbers table, participants were allocated to two equal groups. After induction of anaesthesia, in one group Halothane 1% was administered for the maintenance of anaesthesia in addition with intravenous fentanyl 1.5 microg kg(-1), and for the patients of the other group midazolam with a dose of 0.1 mg kg(-1) and remifentanil infusion by a dose of 0.1 microg kg(-1) min(-1) was administered. The patients were extubated in a unique plan of anaesthesia, using the sign of swallowing as a clinical indicator for extubation of patients. RESULTS: The incidence of laryngospasm was lower in midazolam-remifentanil group (0%) in comparison with halothane-fentanyl group (6.6%). CONCLUSION: The results of our study suggest that remifentanil combined with midazolam in children undergoing eye surgery provided a better condition for extubation of the patients.

Abordaje de la vía aérea en una lactante con linfangioma cervical / Access to the aerial tract in a breastfed child with cervical lymphangioma

Las grandes tumoraciones de cuello se han asociado con dificultades en la intubación. Se realizó la valoración preoperatoria de la vía aérea a través de la historia, el examen físico y los complementarios. Y se consideró una vía aérea difícil y se efectuó inducción con halotano logrando la intubación de la tráquea sin complicaciones. La inducción inhalatoria permitió la intubación endotraqueal en una paciente considerada como una vía aérea difícil.

The big tumors in the neck have being associated with intubation difficulties. We made the presurgery evaluation of the aerial tract through the medical records, physical and complementary examinations. We considered a difficult aerial tract and made the induction with halothane, achieving tracheal intubation without complications. The inhalant intubation allowed the endotracheal intubation in a patient considered as a difficult aerial tract.

Abordaje de la vía aérea en una lactante con linfangioma cervical / Access to the aerial tract in a breastfed child with cervical lymphangioma

Las grandes tumoraciones de cuello se han asociado con dificultades en la intubación. Se realizó la valoración preoperatoria de la vía aérea a través de la historia, el examen físico y los complementarios. Y se consideró una vía aérea difícil y se efectuó inducción con halotano logrando la intubación de la tráquea sin complicaciones. La inducción inhalatoria permitió la intubación endotraqueal en una paciente considerada como una vía aérea difíci

The effect of isoflurane, halothane and pentobarbital on noise-induced hearing loss in mice.

BACKGROUND: Ear surgery using mastoid drills can lead to noise-induced hearing loss (NIHL). We investigated whether inhaled anesthetics or pentobarbital could have protective effects on NIHL in mice. METHODS: Mice were exposed to broad band white noise for 3 h per day for 3 consecutive days, with or without anesthesia, using halothane, isoflurane, or pentobarbital. The hearing level of each mouse was analyzed before exposure, and 1 day, 1, 2, and 3 Wk, and 1 mo after noise exposure by measuring auditory brainstem response thresholds. At 1 Wk after noise exposure, the organ of Corti was stained with a fluorescent isothiocyanate-conjugated phalloidin probe and a TUNEL kit. RESULTS: In the unanesthetized control group, the hearing threshold increased to 77.5 +/- 8.0 dB hearing level (HL) after noise stimulation. In the pentobarbital, isoflurane, and halothane groups, hearing threshold increased to 62.5 +/- 6.3 dB HL, 45.5 +/- 9.8 dB HL, and 39.3 +/- 6.2 dB HL, respectively, with all anesthetized groups of mice showing significantly preserved hearing compared with the control group (P < 0.05). But, in mice anesthetized with pentobarbital, hearing loss was more severe than in those treated with the inhaled anesthetics (P < 0.05). Hair cell survival was reduced in unanesthetized control mice and somewhat reduced in pentobarbital-treated mice, but largely unaffected in mice treated with inhaled anesthetics. CONCLUSIONS: These findings indicate that, while halothane, isoflurane and pentobarbital could protect mice against NIHL and hair cell damage, inhaled anesthetics were more effective.

[Effect of volatile inhalational anesthetics on cerebral blood volume and oxygen status in children].

The investigation evaluated the effect of various volatile anesthetics on cerebral blood volume and oxygen status in sick children at the stage of anesthesia induction. Ninety-two children were distributed into 3 groups: Groups 1 (n = 36) and 2 (n = 24) underwent stepwise induction with halothane and enflurane, respectively. Group 3 (n = 32) had vital capacity rapid inhalation induction with sevoflurane. Cerebral oximetry (NIRS method) was used to measure the content of hydroxyhemoglobin, deoxyhemoglobin, the total level of hemoglobin and to assess regional cerebral tissue saturation (rSO2). Halothane was ascertained to increase cerebral blood volume by 20.5% whereas enflurane and sevoflurane increased it only by 8.8 and 9.0%, respectively. In all cases, the value of rSO2 remained comparatively high, by exceeding the baseline level by 3-5%.

Stimulus-sensitive burst-spiking in burst-suppression in children: implications for management of refractory status epilepticus.

Status epilepticus refractory to sequential trials of multiple medication is a rare but significant problem in children. We describe stimulus sensitivity arising during the treatment of convulsive status epilepticus in children (stimulus-sensitive burst-spiking in burst-suppression). We reviewed retrospectively clinical and EEG features in six children (three months to ten years), with status epilepticus requiring intensive care, in whom tactile, auditory and visual stimulation induced myoclonic jerks and bursts of EEG spikes. Sensitivity was not present at onset, but appeared after 24 hours as myoclonic jerks of the eyes, face and limbs, irrespective of the modality and site of stimulation. These were associated with burst-suppression in the EEG, the induced spiking forming the burst component. Various antiepileptic drugs, including GABAergic and NMDA blockers had no effect, but halogenated agents (used in two patients) abolished the sensitivity. Two children died, but the remainder returned to their previous clinical state. We conclude that stimulus sensitivity may appear in the context of refractory status epilepticus treated with high-dose barbiturates. Outcome may be more favorable than previously reported in adults, mostly in the context of post-anoxic or toxic coma. Evaluation of ventilated children in status epilepticus should include electroclinical assessment using sensory stimulation. If present, the drug regime should be reviewed and halogenated agents considered.

Halothane, an effective infrequently used drug, in the treatment of pediatric status asthmaticus: a case report.

Asthma is the most common chronic disease of childhood. Despite a better understanding of the disease process and its management, status asthmaticus continues to be a life-threatening event. The use of volatile inhaled anesthetics is infrequently reported as adjunctive therapy to conventional treatment of this condition. We report the use of halothane in a mechanically ventilated pediatric patient with life-threatening status asthmaticus who was admitted to the pediatric intensive care unit (PICU) after failing to respond to standard medical therapy and noninvasive positive pressure ventilation. A 12-year-old African American male was seen in the emergency department and treated with intravenous corticosteroids, beta-agonist therapy. He deteriorated rapidly and required endotracheal intubation and mechanical ventilation. Two hours later, the patient developed an acute, severe respiratory acidosis (pH=6.97, PaCO2=171, PaO2=162, BE=1.7). Halothane was started at 2% by using the Siemens Servo 900C anesthesia ventilator. Improvement in both arterial blood gases and exhaled tidal volume were noted 30 minutes after initiation of the anesthetic gas. The patient remained on halothane for a total of 36 hours. No adverse effects associated with the use of halothane were noted. The patient was extubated to BiPAP 16/6, FiO2=0.30 at 68 hours and was discharged home 5 days later.

Anesthesia for removal of inhaled foreign bodies in children.

BACKGROUND: Foreign body aspiration may be a life-threatening emergency in children requiring immediate bronchoscopy under general anesthesia. Both controlled and spontaneous ventilation techniques have been used during anesthesia for bronchoscopic foreign body removal. There is no prospective study in the literature comparing these two techniques. This prospective randomized clinical trial was undertaken to compare spontaneous and controlled ventilation during anesthesia for removal of inhaled foreign bodies in children. METHODS: Thirty-six children posted for rigid bronchoscopy for removal of airway foreign bodies over a period of 2 years and 2 months in our institution were studied. After induction with sleep dose of thiopentone or halothane, they were randomly allocated to one of the two groups. In group I, 17 children were ventilated after obtaining paralysis with suxamethonium. In group II, 19 children were breathing halothane spontaneously in 100% oxygen. RESULTS: All the patients in the spontaneous ventilation group had to be converted to assisted ventilation because of either desaturation or inadequate depth of anesthesia. There was a significantly higher incidence of coughing and bucking in the spontaneous ventilation group compared with the controlled ventilation group (P = 0.0012). CONCLUSION: Use of controlled ventilation with muscle relaxants and inhalation anesthesia provides an even and adequate depth of anesthesia for rigid bronchoscopy.

Anaesthetic experiences in three sets of conjoined twins in King Chulalongkorn Memorial Hospital.

We describe the anaesthetic management for magnetic resonance image scanning, angiography and surgical operations in three sets of conjoined twins (ischiopagus, throracopagus and pygopagus) in King Chulalongkorn Memorial Hospital during 1996-2002. The anaesthetic technique and associated problems are summarized.