Systematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicity.

BACKGROUND: The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy. METHODS: A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded. RESULTS: The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances. CONCLUSIONS: Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low.

Death from Nitrous Oxide.

Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available.

An unusual case of anesthetic abuse by a full-face gas mask.

The authors report a case of sniffing of halothane (Narcotan) by a 32-year-old man, master of pharmacy, through the military full-face gas mask. The liquid halothane had been applied on the scrubber of the gas mask and voluntarily inhaled. The sniffer was found dead in his flat, with the gas mask still fixed and sealed on his face. Because the authors have not encountered any report of such a case in the literature, they present and discuss this case in this article.

Severe myeloneuropathy from acute high-dose nitrous oxide (N2O) abuse.

BACKGROUND: Myeloneuropathy from chronic exposure to nitrous oxide has been described. Nitrous oxide irreversibly alters B(12) activation, causing signs and symptoms of B(12) deficiency. OBJECTIVES: We describe a case of myeloneuropathy secondary to acute use of high-dose nitrous oxide. CASE REPORT: A 24-year-old man presented to the Emergency Department complaining of numbness and tingling of his hands and feet, as well as worsening clumsiness and gait disturbances after escalating use of nitrous oxide in the prior 2 weeks. He was found to have dysmetria, poor proprioception, decreased sensation to vibration and light touch over his extremities, and a mildly positive Romberg sign. Laboratory test values revealed a normal B(12) level but increased methylmalonic acid and homocysteine levels. The patient was admitted to the hospital and started on a course of B(12) injections. He was discharged after 3 days with daily B(12) supplementation. CONCLUSIONS: This case demonstrates myeloneuropathic changes secondary to acute high-dose nitrous oxide exposure.

Defining rules for the identification of critical ventilatory events.

PURPOSE: The automated recognition of critical clinical events by physiological monitors is a challenging task exacerbated by a lack of standardized and clinically relevant threshold criteria. The objective of this investigation was to develop consensus for such criteria regarding the identification of three ventilatory events: disconnection or significant leak in the anesthesia circuit, decreased lung compliance or increased resistance, and anesthetic overdose from inhaled anesthetics. METHODS: We individually administered a structured interview to five expert anesthesiologists to gain insight into the cognitive processes used by clinicians to diagnose ventilatory events and to determine the common heuristics (rules of thumb) used in clinical practice. We then used common themes, identified from analysis of the structured interviews, to generate questions for a series of web-based questionnaires. Using a modified Delphi technique, iterative questionnaire administration facilitated rapid consensus development on the thresholds for the specific rules used to identify ventilatory events. RESULTS: A threshold for 75% agreement was described for each scenario in a healthy ventilated adult. A disconnection or significant leak in the anesthesia circuit is diagnosed with peak airway pressure (< 5 cm H2O or change of 15 cm H2O), ETCO2 (0 mmHg, 40% drop, or value below 10 mmHg for a duration of 20 sec), and inspired-expired volume difference (300 mL). Increased resistance or decreased lung compliance is diagnosed with high peak airway pressure (40 cm H2O or a 20 cm H2O change), asymmetry of capnogram, and changes in measured compliance or resistance. Anesthetic overdose from inhaled anesthetics is diagnosed with high end-tidal anesthetic agent concentration (2 MAC in a patient less than 60 yr of age or 1.75 MAC in a patient over 60 yr of age), low systolic blood pressure (below 60 mmHg), and low modified electroencephalogram (bispectral index or entropy). CONCLUSION: This investigation has provided a set of consensus-based criteria for developing rules for the identification of three critical ventilatory events and has presented insight into the decision heuristics used by clinicians.

Fatal errors in nitrous oxide delivery.

Nitrous oxide continues to be used frequently and the possibility of inadvertent fatal hypoxaemia resulting from technical errors with its administration still exists. A Medline analysis revealed only a few case reports over the last 30 years, and a closed claim analysis only reported 'claims involving oxygen supply lines' predating 1990. The aim of this study was to assess the frequency of nitrous oxide-related catastrophes during general anaesthesia in Germany, Austria, and Switzerland. As nitrous oxide-related anaesthesia casualties are rare but generally prosecuted, they almost invariably attract significant media attention. We scanned mass media archives from April 2004 until October 2006 for nitrous oxide-related disasters during general anaesthesia. This approach detected six incidents which were almost certainly nitrous oxide ventilation-related deaths. Searching non-scientific data bases demonstrates that severe incidents involving oxygen supply lines occurred after 1990, and may be much more frequent than previously thought.

A fatality from sevoflurane abuse.

A case is presented of a 47-year-old man who died as a result of sevoflurane abuse. Sevoflurane was identified and confirmed by headspace gas chromatography-mass spectrometry. The heart blood sevoflurane concentration was 16 mg/L, and the peripheral blood sevoflurane concentration was 8.0 mg/L. No drugs or other volatile substances were found in the heart blood. The medical examiner ruled that the cause of death was cardiac arrhythmia due to sevoflurane toxicity. Cardiomegaly was listed on Part II of the death certificate. The manner of death was undetermined.

Sevoflurane concentrations in blood, brain, and lung after sevoflurane-induced death.

Sevoflurane concentrations in blood, brain, and lung were measured in an individual apparently dying from sevoflurane inhalation. Sevoflurane is a volatile nonflammable fluorinated methyl isopropyl ether inhaled anesthetic, chemically related to desflurane and isoflurane. The incidence of abuse of sevoflurane is lower than that of other drugs of abuse possibly due to its inaccessibility to the general public and less pleasurable and addicting effects. The dead subject was an anesthetist found prone in bed holding an empty bottle of sevoflurane (Ultane). Serum, urine, and liver were screened for numerous drugs and metabolites using enzyme immunoassays and gas chromatography-mass spectrometry. Analysis did not reveal presence of any drug, including ethanol, other than sevoflurane. Sevoflurane was determined by headspace gas chromatography and revealed concentrations of 15 microg/mL in blood and 130 mg/kg in brain and lung. Autopsy revealed pulmonary edema and frothing in the lung, pathological findings associated with death by sevoflurane or hypoxia. The cause of death was ruled as sevoflurane toxicity and the manner of death as accident.

Inhalant abuse.

Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet-underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This clinical report reviews key aspects of inhalant abuse, emphasizes the need for greater awareness, and offers advice regarding the pediatrician's role in the prevention and management of this substance abuse problem.

Health risks and occupational exposure to volatile anaesthetics--a review with a systematic approach.

AIMS AND OBJECTIVES: To provide practicing nurse anaesthetists with evidence based knowledge as to whether they are at risk handling volatile anaesthetics by answering the question: What are the health risks threatening health care personnel occupationally exposed to volatile anaesthetics? BACKGROUND: The interpretations of results from specific scientific studies vary and preliminary research results indicate that occupational exposure to volatile anaesthetics affects the health of operating room personnel. DESIGN: Review of scientific literature with a systematic approach. METHOD: The review included a systematic search in three major databases, a screening process of abstracts/articles followed by a quality assessment of the included studies. The screening process and the quality assessment were done independently by the six reviewers and followed specific protocols. RESULTS: A systematic search of The Cochrane Library, MedLine and CINAHL resulted in a screening of 413 abstracts of which 31 articles were assessed for quality, all done independently by the reviewers. Finally, the reviewers agreed upon how to interpret the results of the assessed articles. CONCLUSIONS: The 31 articles assessed covered areas such as genotoxic effects, neurobehavioural effects, immunology, and general health effects. In the scientific literature reviewed there is no evidence of occupational exposure to volatile anaesthetics either being associated with health risks or being harmless. Studies indicating a potential health risk are all investigating circumstances ignorant of modern environmental regulations and/or with no scavenging equipment. RELEVANCE TO CLINICAL PRACTICE: Although no answer has been given, this review illuminates the methodological difficulties encountered in designing studies. The result of this review further stresses the need for scientific knowledge in this area and enhances the extensive use of scavenging equipment.

The distribution of sevoflurane in a sevoflurane induced death.

The distribution of sevoflurane (fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether) in blood, urine, liver, kidney, vitreous humor, and tracheal aspirate is presented from a subject with a sevoflurane induced death. Sevoflurane is a nonflammable general anesthetic administered by inhalation of vaporized liquid. Although general inhalation anesthetics have the potential to be fatal if not properly administered, the incidence of abuse is minute in comparison to other illicit drugs. Currently, there are no citations in the literature defining the body distribution of sevoflurane in a sevoflurane induced death. The decedent was found lying in a bed with an oxygen mask containing a gauze pad secured to his face. Three empty bottles and one partially full bottle of Ultane (sevoflurane) were found with the body in addition to two pill boxes containing a variety of prescription and non-prescription drugs. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatographic, colorimetric and immunoassay techniques. Analysis of biological specimens from the deceased revealed the presence of: amphetamine, caffeine, pseudoephedrine, nicotine, nicotine metabolite, and valproic acid. Sevoflurane concentrations were determined by headspace gas chromatography with flame ionization detection and revealed concentrations of 26.2 microg/mL in the blood, 105 microg/mL in the urine, 31.9 microg/mL in the tracheal aspirate, 86.7 microg/mL in the vitreous humor, 30.8 mg/kg in the liver, and 12.8 mg/kg in the kidney. The decedent had pathologies consistent with respiratory suppression including pulmonary atelectasis, pulmonary edema, and neck vein distention. The official cause of death was respiratory suppression by sevoflurane and the manner of death was unclear.

Myeloneuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine levels.

A 23-year-old patient developed diffuse paresthesias and sensory loss. He had mildly reduced serum vitamin B12 (B12) concentration with unusually high levels of methylmalonic acid (MMA) and homocysteine and no evidence of B12 malabsorption. Following parenteral B12 administration, his neurological deficit promptly resolved and B12 and MMA levels normalized, but elevated levels of homocysteine persisted. One year later, he admitted to inhaling nitrous oxide (N2O). After halting N2O abuse his homocysteine level normalized. This case demonstrates the importance of serum homocysteine level measurements in cases of suspected N2O toxicity [corrected].

Toxicity of compound A to C6 rat glioma cells.

The volatile anesthetic, sevoflurane, undergoes degradation by soda lime to form Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene). Compound A is toxic in vivo with the kidney being the primary target. However, peripheral neuropathy was recently reported in a group of healthy volunteers who received sevoflurane. The present study was undertaken to evaluate the toxicity of Compound A to neural cells. Rat glioma C6 cells were grown in T25 flasks in 5 mL of DMEM/F12 were exposed to Compound A, and the viability of cells was determined at various time points by trypan blue exclusion. Within 1 h after the addition of 10 microL of Compound A, the fragmentation of cell processes and rounding of cell bodies became apparent. The cellular degeneration progressed over time resulting in the loss of all viable cells from the cultures within 6 h. Even brief exposures to Compound A ranging from 5 to 30 min resulted in massive cell death observed 24 h later, and the toxicity was concentration-dependent. These preliminary experiments indicate that Compound A is a potent toxin to glial cells in vitro. A plausible mechanism for this toxicity entails the depletion of intracellular glutathione resulting in oxidative stress of the cells. However, the relatively high doses of Compound A used to observe its effects do not support the toxicity of Compound A to glial cells under clinical conditions.