Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 9744689

Halothane hepatitis.

J Neuberger
View original source ↗Export metadata ↓

Abstract

Halothane, an effective and usually safe anaesthetic agent, is rarely associated with the development of fulminant hepatic failure. Guidelines have been developed to reduce the probability of a patient developing halothane hepatitis. However, cases continue to occur and, in some cases, the guidelines have been ignored. Stricter adherence to the guidelines will reduce, but not totally prevent, further cases from occurring. Once halothane hepatitis has developed, there are no specific treatments and liver replacement may be required. Halothane hepatitis is a paradigm for immune mediated adverse drug reactions. The mechanism appears to be related to development of sensitization to both autoantigens (including CYP2D6) and halothane-altered liver cell determinants.

Explore related subjects

Anesthetics, InhalationChemical and Drug Induced Liver InjuryGuideline AdherenceHalothaneHumansLiver TransplantationJournal ArticleComment

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J Neuberger. 1998. Halothane hepatitis.. https://pubmed.ncbi.nlm.nih.gov/9744689/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1999

Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer.

In spite of several reports about suppressive effects of volatile anesthetics on somatosensation, their neuronal mechanisms are largely unknown. The present study investigates somatosensory impulse transmission at the thalamic level in rats under varied concentrations of isoflurane by recordings of neuronal responses to mechanical stimulation of the body surface. Single-unit recordings of thalamo-cortical relay neurons (TCNs, third order neurons; n=28) and presumed trigemino-thalamic fibers (TTFs, second order neurons; n=7) were performed in the ventral posteromedial nucleus. Functional response characteristics were quantified following defined tactile stimulation (trapezoidal or vibratory deflection of sinus hairs or fur) applied to the neuronal receptive fields. End-tidal isoflurane concentration was increased in steps of 0.2% between 0.6% (baseline) and 2.0%. The response activity in all TCNs studied was suppressed in a dose-dependent manner (2.0% isoflurane decreased responses to 3. 5+/-1.1% of baseline; mean+/-S.E.M.); the response activity in TTFs was much less affected (decrease to 55.0+/-8.2%). Suppression of ongoing activity, however, was similar for both, TCNs and TTFs. Furthermore, in TCNs, the response characteristics changed with increasing isoflurane between 1.0% and 1.8%: tonic and sustained responses were converted to phasic on-responses. In contrast, the tonic and sustained response characteristics of TTFs were preserved even at higher isoflurane concentrations. The results indicate that isoflurane attenuates the output of somatosensory signals in the specific nucleus of the rat's thalamus, while its input is only marginally affected. The observed changes of thalamic neuronal response characteristics, at least in part, may cause the loss in sensory discrimination observed during general anesthesia.

Anesthetics, Inhalation↗
PubMed1999

Effects of halothane on renal hemodynamics and interstitial nitric oxide in rabbits.

The effects of halothane on renal hemodynamics and the nitric oxide (NO)-guanylate cyclase signaling pathway were examined in anesthetized rabbits using a renal microdialysis method. Halothane (0.5 and 2 vol%) caused dose-dependent decreases in blood pressure, renal blood flow and the renal interstitial concentrations of guanosine 3',5'-cyclic monophosphate (cGMP) or nitrate (NO2)/nitrite (NO3). Sodium nitroprusside (20 microg kg(-1) min(-1), i.v.) under the inhalation of halothane (2 vol%) increased the renal interstitial concentration of cGMP. L-Arginine (priming dose, 300 mg kg(-1) 10 min(-1); sustaining dose, 50 mg kg(-1) min(-1), i.v.) did not reverse halothane-induced reductions of cGMP and NO2/NO3. These findings demonstrate that halothane caused a renal vasoconstriction and inhibited the NO-guanylate cyclase signaling pathway in the kidney. Moreover, it is possible that the renal hemodynamic responses to halothane might have been induced, in part, through this inhibition. Finally, it can be assumed that halothane did not interfere with the activation process of guanylate cyclase by NO.

Anesthetics, Inhalation↗
PubMed1999

Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin.

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly understood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transition of bovine serum albumin. We find that halothane (0.6-10 mM) stabilizes the folded state of this protein, increasing its transition midpoint temperature from 62 to 71 degrees C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the thermally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change DeltaH for unfolding of 170 kcal/mol, the increase from 62 to 71 degrees C corresponds to an additional Gibbs energy of stabilization (DeltaDeltaG) due to halothane of more than 4 kcal/mol. Analysis of the dependence of DeltaDeltaG on halothane concentration shows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concentrations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown to be stabilized by an inhalational anesthetic.

Anesthetics, Inhalation↗