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Cost-effectiveness Analysis of Stocking Dantrolene in Ambulatory Surgery Centers for the Treatment of Malignant Hyperthermia
Abstract
Malignant hyperthermia (MH) is a rare hypermetabolic syndrome of the skeletal muscle and a potentially fatal complication of general anesthesia. Dantrolene is currently the only specific treatment for MH. The Malignant Hyperthermia Association of the United States has issued guidelines recommending that 36 vials (20 mg per vial) of dantrolene remain in stock at every surgery center. However, the cost of stocking dantrolene in ambulatory surgery centers has been a concern. The purpose of this analysis is to assess the cost-effectiveness of stocking dantrolene in ambulatory surgery centers as recommended by the Malignant Hyperthermia Association of the United States.
A decision tree model was used to compare treatment with dantrolene to a supportive care-only strategy. Model assumptions include the incidence of MH, MH case fatality with dantrolene treatment and with supportive care-only. Sensitivity analyses were performed to assess the robustness of the estimated cost-effectiveness.
The estimated annual number of MH events in ambulatory surgery centers in the United States was 47. The incremental effectiveness of dantrolene compared with supportive care was 33 more lives saved per year. The incremental cost-effectiveness ratio was $196,320 (in 2010 dollars) per life saved compared with a supportive care strategy. Sensitivity analysis showed that the results were robust for the plausible range of all variables and assumptions tested.
The results of this analysis suggest that stocking dantrolene for the treatment of MH in ambulatory surgery centers as recommended by the Malignant Hyperthermia Association of the United States is cost-effective when compared with the estimated values of statistical life used by U.S. regulatory agencies.
... Malignant Hyperthermia Cart on Maternity Units centers). 4 However, maternity units uncommonly use MHtriggering agents. For example, an institution that delivers 6,000 babies a year and has a 30% cesarean delivery rate and a 5% general anesthesia rate will use general anesthesia less than 100 times a year. ...
... Estimated maternal mortality with no dantrolene treatment is 80% and with dantrolene treatment available within 10 min is 10%. 4 The calculated number of annual lives saved is 0.33 (80,427/170,968 times 70% (i.e., 80% minus 10%). ...
... For example, a previous study found that stocking dantrolene is of cost benefit in a small ambulatory surgical center that performs 10 triggering anesthetics a day (i.e., 2,000 to 3,000 anesthetics per year). 4 However, the number of triggering anesthetics is at least an order of magnitude lower in maternity units. For example, even a maternity unit with 10,000 deliveries per year would be expected to perform at most 200 to 300 general anesthetics per year. ...
Background:
The Malignant Hyperthermia Association of the United States recommends that dantrolene be available for administration within 10 min. One approach to dantrolene availability is a malignant hyperthermia cart, stocked with dantrolene, other drugs, and supplies. However, this may not be of cost benefit for maternity units, where triggering agents are rarely used.
Methods:
The authors performed a cost-benefit analysis of maintaining a malignant hyperthermia cart versus a malignant hyperthermia cart readily available within the hospital versus an initial dantrolene dose of 250 mg, on every maternity unit in the United States. A decision-tree model was used to estimate the expected number of lives saved, and this benefit was compared against the expected costs of the policy.
Results:
We found that maintaining a malignant hyperthermia cart in every maternity unit in the United States would reduce morbidity and mortality costs by $3,304,641 per year nationally but would cost $5,927,040 annually. Sensitivity analyses showed that our results were largely driven by the extremely low incidence of general anesthesia. If cesarean delivery rates in the United States remained at 32% of all births, the general anesthetic rate would have to be greater than 11% to achieve cost benefit. The only cost-effective strategy is to keep a 250-mg dose of dantrolene on the unit for starting therapy.
Conclusions:
It is not of cost benefit to maintain a fully stocked malignant hyperthermia cart with a full supply of dantrolene within 10 min of maternity units. We recommend that hospitals institute alternative strategies (e.g., maintain a small supply of dantrolene on the maternity unit for starting treatment).
... It is difficult to estimate the exact incidence of MH. 20 It is known to vary between 0.3 and 2 for every 100,000 general anesthesias administered. 3,5,12,[21][22][23] For the purpose of this assessment, an intermediate incidence of 1 case for every 100,000 general anesthesias with trigger drugs was used. ...
... Aderibigbe et al 22 On the other hand, Ho et al assessed the cost-benefit relationship of keeping dantrolene stocks in maternity units. The analysis showed that costs associated with keeping a MH cart with a full supply of dantrolene within 10 minutes of a maternity unit exceeded the benefits. ...
Introduction:
Malignant hyperthermia (MH) is an acute syndrome triggered by certain anesthetic medications. Dantrolene is the only specific treatment for MH crises. Without treatment, lethality may be as high as 80%. In Colombia, it is not mandatory to keep dantrolene supplies in stock.
Objective:
To establish the cost-benefit ratio, from the perspective of healthcare institutions, of keeping dantrolene supplies in stock in the operating theater.
Methods:
Using a decision tree, a Monte Carlo simulation was run with 10,000 scenarios to determine the median annual cost of keeping full or partial stocks (36 or 12 vials x 20 mg, respectively) of dantrolene. For the option of not keeping supplies in stock, the cost threshold was calculated where the expected value of both alternatives of the decision tree is equalized. Indifference curves were constructed for complete and partial supplies.
Results:
The median annual cost was estimated at 6.6 million Colombian pesos (COP) for full dantrolene supplies, and at COP 2.2 million for partial supplies. The median economic consequence threshold for 1 death due to the unavailability of dantrolene was estimated at COP 18.5 million for full supplies, and at COP 57.0 million for partial supplies.
Conclusion:
If, as a result of the unavailability of dantrolene, the economic consequences of a death due to MH exceed the threshold of COP 57.0 or COP 18.5 million, the purchase of full or partial stocks, respectively, is justified.
... [7] However, the costs involved with continuous temperature monitoring and stocking dantrolene owing to its 3year shelf-life limit, as well as the relatively high cost of the drug can also be issues that may govern the formulation of public health policies. [8,9] Further, the paucity of epidemiologic data on MH leads to uncertainty regarding its true incidence, which limits analysis of cost-effectiveness. [9] Thus, the primary objective of this systematic review and metaanalysis is to determine the incidence of MH in patients undergoing general anesthesia. ...
... [8,9] Further, the paucity of epidemiologic data on MH leads to uncertainty regarding its true incidence, which limits analysis of cost-effectiveness. [9] Thus, the primary objective of this systematic review and metaanalysis is to determine the incidence of MH in patients undergoing general anesthesia. Further, this review will attempt to evaluate trends in the incidence of MH. ...
Background:
Malignant hyperthermia (MH) continues to be of potential concern for clinicians whenever inhalational anesthetic agents or succinylcholine are used, because MH is a potentially fatal metabolic disorder.
Methods:
A systematic and comprehensive search will be performed using MEDLINE, EMBASE, and Google Scholar, for studies published up to November 2017. Peer-reviewed prospective cohort studies, retrospective cohort studies, and cross-sectional studies or reports issued by government organizations reporting the incidence or prevalence of MH will be eligible for inclusion. The quality of included studies will be assessed using the Newcastle-Ottawa scale and the modified risk of bias tool. Heterogeneity of estimates across studies as well as publication bias will be assessed. This systematic review and meta-analysis will be performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. All statistical analyses will be conducted using the Stata SE version 15.0.
Results:
The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.
Conclusion:
To our knowledge, this systematic review and meta-analysis will be the first to evaluate existing research on the incidence of MH. Our study will provide an overall estimate of the incidence of MH. Subgroup analysis will assess the incidence of MH according to age, gender, geographical region, race, and the provoking agent if possible. The review will benefit patients, healthcare providers, and policymakers.
Ethics and dissemination:
Ethical approval and informed consent are not required, as the study will be a literature review and will not involve direct contact with patients or alterations to patient care.
Trial registration number:
The protocol for this review has been registered in the PROSPERO network (registration number: CRD42017076628).
... The effective dose to reverse the crisis is directly dependent on the individual's degree of susceptibility to MH, amount and time of exposure to the triggering agent, and time elapsed between the onset of the crisis and initiation of treatment ( Table 1). The dose of intravenous DS administered to pediatric patients was the same as that administered to adults [4,43,44]. ② Ryanodex ® is simplified and rapidly reconstituted to prepare a single vial within 10 s [1,4]. The time to administer a 2.5 mg/kg loading dose of Ryanodex ® for a 100 kg patient is 1 min compared to > 22 min for other approved formulations [22,45]. ...
Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH) and was adopted as the primary therapeutic drug after intravenous administration. However, it is difficult to administer DS intravenously to manage MH. MH is life-threatening, pharmacogenomically related, and induced by depolarizing neuromuscular blocking agents or inhalational anesthetics. All anesthesiologists should know the pharmacology of DS. DS suppresses Ca2+ release from ryanodine receptors (RyRs). RyRs are expressed in various tissues, although their distribution differs among subtypes. The anatomical and physiological functions of RyRs have also been demonstrated as effective therapeutic drugs for cardiac arrhythmias, Alzheimer’s disease, and other RyR-related diseases. Recently, a new formulation was introduced that enhanced the hydrophilicity of the lipophilic DS. The authors summarize the pharmacological properties of DS and comment on its indications, contraindications, adverse effects, and interactions with other drugs by reviewing reference articles.
... Our primary hypothesis was confirmed that in over 95% of cases, dantrolene was prescribed for diagnoses other than MH. Although the lifesaving benefit of having dantrolene immediately available for the treatment of MH in operative settings is wellestablished [46], the cost-effectiveness of dantrolene for other syndromes with similar hypermetabolic symptoms remains uncertain. The theoretical rationale for the use of dantrolene in these syndromes other than MH derives by analogy from its proposed mechanism of action in MH; namely, that regardless of the various triggers that may cause symptoms, e.g., antipsychotics in NMS, ambient heat in heatstroke, or inflammatory response in sepsis, dantrolene may reduce hypermetabolic activity in muscle and the resulting systemic symptoms by sequestration of intracellular calcium in the sarcoplasmic reticulum. ...
Background
Intravenous dantrolene is often prescribed for hypermetabolic syndromes other than the approved indication of malignant hyperthermia (MH). To clarify the extent of and indications for dantrolene use in conditions other than MH, we sought to document current practices in the frequency, diagnoses, clinical characteristics and outcomes associated with dantrolene treatment in critical care settings.
Methods
Inpatients receiving intravenous dantrolene from October 1, 2004 to September 30, 2014 were identified retrospectively in the U.S. Veterans Health Administration national database. Extracted data included; diagnoses of hypermetabolic syndromes; triggering drugs; dantrolene dosages; demographics; vital signs; laboratory values; in-hospital mortality; complications; and lengths of stay. Frequency and mortality of patients who did not receive dantrolene were obtained in selected diagnoses for exploratory comparisons.
Results
Dantrolene was administered to 304 inpatients. The most frequent diagnoses associated with dantrolene treatment were neuroleptic malignant syndrome (NMS; N = 108, 35.53%) and sepsis ( N = 47, 15.46%), with MH accounting for only 13 (4.28%) cases. Over half the patients had psychiatric comorbidities and received psychotropic drugs before dantrolene treatment. Common clinical findings in patients receiving dantrolene included elevated temperature (mean ± SD; 38.7 ± 1.3 °C), pulse (116.33 ± 22.80/bpm), respirations (27.75 ± 9.58/min), creatine kinase levels (2,859.37 ± 6,646.88 IU/L) and low pO 2 (74.93 ± 40.16 mmHg). Respiratory, renal or cardiac failure were common complications. Mortality rates in-hospital were 24.01% overall, 7.69% in MH, 20.37% in NMS and 42.55% in sepsis, compared with mortality rates in larger and possibly less severe groups of unmatched patients with MH (5.26%), NMS (6.66%), or sepsis (41.91%) who did not receive dantrolene.
Conclusions
In over 95% of cases, dantrolene administration was associated with diagnoses other than MH in critically-ill patients with hypermetabolic symptoms and medical and psychiatric comorbidities. Exploratory survey data suggested that the efficacy and safety of dantrolene in preventing mortality in hypermetabolic syndromes other than MH remain uncertain. However, randomized and controlled studies using standardized criteria between groups matched for severity are essential to guide practice in using dantrolene.
... The study by Aderibigbe et al. conducted in the United States in outpatient facilities performing general anesthesias for oneday surgery has even demonstrated potential financial benefits associat ed with the possession of dantrolene [13]. Accord ing to the authors, if each surgical clinic had a stock of 36 vials of dantrolene, 33 deaths could be avoid ed annually; the incremental costeffectiveness ra tio (iCer) has been calculated at about $200,000 for each patient saved. ...
Introduction:
Malignant hyperthermia (MH) is a life-threatening syndrome caused by sudden skeletal muscle hypermetabolism in response to inhalation anaesthetics and depolarising relaxants. The estimated incidence of MH is between 1 : 10,000 and 1 : 250,000 anaesthetic procedures. In Poland the incidence of MH is unknown. Dantrolene is imported as a life-saving drug and temporally authorised for sale. The aim of the study is to assess the incidence of MH and access to dantrolene in the Mazovia Province.
Methods:
Anonymous questionnaires were sent to anaesthesia departments in the Mazovia Province after prior contact by phone and e-mail. The survey was approved by the local ethical review board.
Results:
Completed surveys were received from 60 respondents which represents 72% of anaesthesiology departments in Mazovia. In the last 5 years there have been 4 episodes of MH in the Mazovia Province. Three patients survived the MH crisis. In a centre that did not have access to dantrolene, the patient died. Dantrolene is found only in 11 (18.3%) anaesthesiology departments in Mazovia. Only 6 (10%) hospitals are able to administer dantrolene within 5 minutes of suspecting MH crisis, while 5 centres may receive it after a few days. Only 38% of units have an algorithm for dealing with MH crisis in the operating theatres.
Conclusions:
MH is rare, but if untreated, it can be fatal. Therefore prompt diagnosis and treatment are crucial to avoid fatal outcome. Every centre using inhalational anaesthetics and/or succinylcholine should have dantrolene. To ensure the safety of our patients, we must be better prepared.
... Although our patient showed a good clinical response to the discontinuation of the triggering agent and active cooling, the Malignant Hyperthermia Association of the United States recommends that all facilities where malignant hyperthermia-triggering anesthetics and depolarizing muscle relaxants are administered should stock dantrolene [14]. However, dantrolene is an expensive orphan drug and has a short lifespan; thus, dantrolene is still limitedly available and the routine preparation of dantrolene may not be possible in all hospitals [15]. Therefore, a systematic connection with other medical centers that have dantrolene in stock, or a national orphan drug center and rapid transfer system, would be very important. ...
Malignant hyperthermia is an extremely rare, potentially lethal disorder that occurs in susceptible patients who are exposed to triggering agents such as volatile anesthetic gases or depolarizing muscle relaxants. The clinical manifestations of malignant hyperthermia include hypermetabolism, hyperthermia, hypercapnia, and sustained skeletal muscle rigidity, which result in cardiac arrest, brain damage, and death. It is associated with a high morbidity and mortality rate if not recognized immediately and treated appropriately. We report a case of suspected malignant hyperthermia in a young male patient undergoing axillary osmidrosis surgery.
... Utilizando um exemplo na área da anestesiologia, Aderibigbe et al procederam a um estudo de custo-efectividade com o objectivo de avaliar se seria custoefectivo armazenar dantroleno em centros de cirurgia de ambulatório para tratamento de hipertermia maligna. 6 No que respeita à diferença nacional de custos entre alternativas, os autores concluíram que o armazenamento de dantroleno se associaria a mais $6 458 940 por comparação com o não armazenamento. Por outro lado, os autores também estimaram que o armazenamento de dantroleno se associaria a um saldo de 32,9 vidas adicionais salvas por ano. ...
RESUMO Os estudos de custo-efectividade e custo-utilidade correspondem a tipos de avaliação económica completa, pelo que procuram informar simultaneamente acerca dos custos e consequências das alternativas em estudo. Nos estudos de custo-efectividade, as consequências são expressas sob a forma de unidades naturais de efectividade (e.g., anos de vida ganhos). Nestes estudos, a comparação de alternativas tem por base a determinação de razões de custo-efectividade incremental (ICER) (razão entre a diferença de custos médios/estimados e a diferença de efectividades médias/estimadas)-uma alternativa é considerada custo-efectiva quando o seu ICER é inferior ao limiar de aceitabilidade definido. Ou seja, quando se considera que a alternativa acarreta ganhos de efectividade a custos pelos quais a sociedade está disposta a pagar. Por sua vez, nos estudos de custo-utilidade, as consequências são expressas sob a forma de unidades de efectividade ajustadas para as preferências dos indivíduos ou da sociedade. Os quality-adjusted life years (QALYs) constituem um exemplo de tais medidas, incorporando simultaneamente informação relativa à sobrevida média e à qualidade de vida subjacente ao estado de saúde resultante. Nos estudos de custo-utilidade, a comparação de alternativas tem por base a determinação de razões de custo-utilidade incremental, cujo método de cálculo e interpretação são similares aos dos ICER.
ABSTRACT Cost-effectiveness and cost-utility analyses are types of full economic evaluations, simultaneously informing on costs and outcomes of different alternatives. In cost-effectiveness analyses, health outcomes are expressed in natural effectiveness units (e.g., life years gained). In these studies, comparison of two or more alternatives is based on incremental cost-effectiveness ratios (ICER) (ratio of the (i) difference between average/expected costs for each alternative, and the (ii) difference between the average/expected effectiveness of each alternative)-an alternative is considered to be cost-effective when its ICER is lower than the defined willingness-to-pay threshold. On the other hand, in cost-utility analyses, health outcomes are expressed in effectiveness units adjusted for individual or societal preferences. Therefore, in these studies, outcomes are frequently expressed as quality-adjusted life years (QALYs). In fact, QALYs simultaneously incorporate information on the average/expected life expectancy and quality of life following an intervention. In cost-utility analyses, comparison of different alternatives is based on incremental cost-utility ratios, with calculation and interpretation similar to those of ICER. INTRODUÇÃO Este é o segundo artigo de uma série que tem por objectivo discutir a avaliação crítica de estudos de avaliação económica. Na publicação anterior, 1 foram apresentadas as principais tipologias dos estudos de avaliação económica, as quais podem ser enquadradas em dois grandes grupos-(i) os estudos de avaliação económica parcial/incompleta, e (ii) os estudos de avaliação económica completa. Enquanto os primeiros apenas consideram custos, os últimos têm em
... This is because the interventions recommended are not overly burdensome or costly. 37,38 For example, malignant hyperthermia susceptibility is a disease susceptibility phenotype and therefore does not reliably manifest detectable signs and symptoms (even in the setting of a known volatile anesthetic). The clinical diagnostic test is invasive and expensive (caffeine-halothane contraction test, which requires muscle biopsy). ...
Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequencing results in a diagnostic setting. For these reasons, clinicians should employ an evaluation and long-term management strategy that accounts for both the increased disease risk associated with a secondary finding and the lower positive predictive value of a screening result compared to an indication-based testing result. Here we describe an approach to the clinical evaluation and management of an individual who presents with a secondary finding. This approach enumerates five domains of evaluation—(1) medical history, (2) physical exam, (3) family history, (4) diagnostic phenotypic testing, and (5) variant correlation—through which a clinician can distinguish a molecular finding from a clinicomolecular diagnosis of genomic disease. With this framework, both geneticists and non-geneticist clinicians can optimize their ability to detect and mitigate genomic disease while avoiding the pitfalls of overdiagnosis. Our goal with this approach is to help clinicians translate secondary findings into meaningful recognition, treatment, and prevention of disease.
... 5e7 The product data sheet describes an initial dose of 1 mg kg À1 and a maximum dose of 10 mg kg À1 , 8 but most recent guidelines and reviews on the subject recommend a higher initial dose and no cumulative ceiling. 9e11 Despite its efficacy and the demonstration that stocking dantrolene is cost-effective even at ambulatory surgery centres, 12 the pressures imposed by limited healthcare resources mean that advice concerning the minimum locations where dantrolene needs to be stocked and the minimum quantity to be stocked is frequently sought. The pharmaco-economic model for dantrolene is unusual as it is relatively expensive, is not often used, has a limited shelf life, and might expire unused because MH reactions are rare. ...
Faced with a malignant hyperthermia crisis, the immediate access to sufficient dantrolene is essential to achieve the best possible outcome for the patient. However, malignant hyperthermia crises are rare, and there may be administrative pressures to limit the amount of dantrolene stocked or, in some countries, not to stock dantrolene at all. There are no published guidelines to support anaesthetic departments in their effort to ensure availability of sufficient dantrolene for the management of malignant hyperthermia crises. After a literature review that confirmed a lack of clinical trials to inform this guideline, we undertook a formal consensus development process, in which 25 members of the European Malignant Hyperthermia Group participated. The consensus process used a modified web-based Delphi exercise, in which participants rated the appropriateness of statements that covered the dosing regimen for dantrolene in a malignant hyperthermia crisis, the types of facility that should stock dantrolene, and the amount of dantrolene that should be stocked. The resulting guidelines are based on available evidence and the opinions of international malignant hyperthermia experts representing a large group of malignant hyperthermia laboratories from around the world. Key recommendations include: the dosing regimen of dantrolene should be based on actual body weight, dantrolene should be available wherever volatile anaesthetics or succinylcholine are used, and 36 vials of dantrolene should be immediately available with a further 24 vials available within 1 h.
... The low incidence of MH crisis and the low utilization of general anesthesia and triggering agents in obstetrics would not make stocking dantrolene policy cost-beneficial. Similar concerns have also been raised in ambulatory surgery centers but two recent studies support the dantrolene stocking policy in these centers [3,23]. Of note, the prevalence of MH susceptibility of 0.81 per 100,000 cesarean deliveries (or 1 in 123,456 cases) reported in our study, similar to the prevalence reported in non-obstetrical surgery inpatients, suggests that stocking dantrolene in maternity units is justified. ...
Abstract Background The cost-benefit of stocking dantrolene in maternity units for treating malignant hyperthermia (MH) has been recently questioned because of the low incidence of MH crisis in the general population and the low utilization of general anesthesia in obstetrics. However, no study has examined the prevalence of MH susceptibility in obstetrics. This study aimed to assess the prevalence of MH diagnosis and associated factors in obstetric patients. Methods Data for this study came from the National Inpatient Sample from 2003 to 2014, a 20% nationally representative sample of discharge records from community hospitals. A diagnosis of MH due to anesthesia was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification code 995.86. MH prevalence was estimated according to the delivery mode and patient and hospital characteristics. Results During the 12-year study period, 47,178,322 delivery-related discharges [including 15,175,127 (32.2%) cesarean deliveries] were identified. Of them, 215 recorded a diagnosis of MH, yielding a prevalence of 0.46 per 100,000 [95% confidence interval (CI), 0.40 to 0.52]. The prevalence of MH diagnosis in cesarean deliveries was 0.81 per 100,000 (95% CI, 0.67 to 0.97), compared with 0.29 per 100,000 (95% CI, 0.23 to 0.35) in vaginal deliveries (P
... Selection bias, selective reporting, and recall bias affected most of these investigations.We did not perform a cost-effectiveness study, but dantrolene's cost effectiveness in ambulatory surgery centers has been previously reported. 72 Given our new data, investigators may wish to pursue additional cost-benefit analyses, although MH incidence is still difficult to determine. 67,73,74 Conclusions This study presents evidence that succinylcholine is used frequently in many anesthetizing and sedating locations, including for cases in which difficult mask ventilation is encountered. ...
What we already know about this topic:
WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality.
Methods:
The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given.
Results:
Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities.
Conclusions:
Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.
... The authors did not conduct a health economic analysis of the cost benefit of stocking dantrolene in this context, instead referring to a previous health economic analysis of the wider question of whether it is cost-effective to stock dantrolene in ambulatory surgery centers where any MH-triggering drug is likely to be available. 2 The context of the study is conflicting recommendations from the Malignant Hyperthermia Association of the United States, which advocates availability of dantrolene, 3 and from the Society for Ambulatory Anesthesia, which suggests availability of dantrolene is not mandatory. 4 In attempting to address the issues at stake, Larach et al. 1 have completed a gargantuan task. ...
... However, dantrolene is expensive and has a short life span; thus, routine preparation of dantrolene may not be cost effective [2]. In previous reports, it was noted that many hospitals were not prepared to provide the recommended dose of 36 vials of dantrolene [3]. ...
... In healthcare, the concept of CEA was first proposed by Weinstein and Stason in 1977 [25]. The units of effectiveness measure in CEA can be : number of successful cases treated, number of cases screened or prevented, number of lives saved or number of life years gained [26][27][28][29][30][31][32][33]. For ease of comparing and ranking more than two alternatives in CEA, the notion of costeffectiveness ratio (CER) has been adopted [34,35]. ...
In its broadest term, economic evaluation (EE) is a comparative analysis of the input (costs) and the output (consequences, outcomes) of two or more alternatives to see if they are economically beneficial or feasible. The earliest form of economic evaluation took place in mid-19th century and since then; three main forms of EE have evolved which are employed in various settings: cost-benefit analysis (CBA), cost-effectiveness analysis (CEA) and cost-utility analysis (CUA). Intended as a primer reading for clinicians, this article starts with the fundamental concepts of economics (e.g., costs, benefits, supply and demand, utilities and efficiency) and then combine them into principles for each tool for EE. The article will present a narrative critique of each EE in the context of modern healthcare system. As a conclusion, the article will mention some of the major challenges of these EE tools plus the role of sensitivity analysis.
Purpose:
The National Remote Emergency System for Malignant Hyperthermia (MH-NRES) is an applet in China, designed to help anesthesiologists manage MH crisis. However, there is limited information about encountered difficulties in dealing with MH among Chinese anesthesiologists. The purpose of the study was to explore the current competency and encountered difficulties in the management of MH, as a key first step for assessing the potential user needs to develop the MH-NRES.
Methods:
The hospitals of different levels in different provinces across China were invited to participate in an online survey from November to December 2021. Anesthesiologists completed the online questionnaire containing four sections including demographic information, knowledge, competency, and continuing education about MH.
Results:
A total of 1357 valid questionnaires were completed from anesthesiologists, most respondents (66.7%, n = 905) correctly answered the MH trigger drugs included volatile anesthetics and succinylcholine. However, most respondents (77.0%, n = 1045) did not know that the recommended initial dose of domestic dantrolene. Up to 83.9% (n = 1138) stated that their hospitals did not store dantrolene for MH emergency. More than half of respondents thought that it would take more than one hour to obtain dantrolene in emergency. Less work experiences, lower levels of hospital and educations and professional titles were associated with lower competency scores in managing MH. Only 31.0% (n = 936) reported that their hospital had ever conducted MH continuing education curricula. Scenario simulation is the training method that most interests the participants (79.0%, n = 1072) but a whopping 46.9% (n = 637) never received simulation.
Conclusion:
The study indicated that difficulty in obtaining dantrolene, lack of competency in management of MH, difficulty in obtaining professional help, and poor teamwork were the main problems of most anesthesiologists in face of MH.
The goal of this chapter is to discuss the demand of taxpayers, employers, and employees that medicine deliver better value. Physicians need evidence-based medicine to establish which interventions are truly beneficial and modern management techniques to implement those interventions optimally. 1. Perioperative interventions are investments, each with its costs and, it is hoped, its benefits. The benefits of perioperative interventions are often difficult to quantify in precise dollar amounts (e.g., pain relief). 2. Three ways of measuring the benefits of interventions are by improved clinical results (i.e., effects), by increased quality-adjusted life-years (QALYs), or by monetary benefit. 3. Any new intervention being considered must be evaluated in comparison with the best existing alternative. As a result, the fundamental concept is the incremental cost-to-effectiveness ratio. 4. Because of the multiplicity of health-care stakeholders (i.e., patients, providers, payers, and society as a whole), an economic study in health-care must specify ahead of time and be consistent in its point of view. 5. Costs of perioperative interventions are direct, indirect, and intangible. Direct costs are the easiest to define and quantify, but vary depending on the costing method used. Direct costs decrease over time, because of competition, the learning curve, technological progress, work process redesign, and the bundling of interventions. 6. Much more attention should be directed toward identifying and addressing barriers to implementation of beneficial interventions. These barriers include lack of awareness (the physician does not know about the new intervention), of familiarity (knows intervention exists but not the details), of agreement (physician does not agree with proposed intervention), of self-efficacy (does not think they can do it), of outcome expectancy (does not think it will work), as well as system factors not allowing successful implementation.
Malignant hyperthermia (MH) is a rare but potentially lethal skeletal muscle disorder affecting calcium release channels. It is inherited in a mendelian autosomal dominant pattern with variable penetration. The initial clinical manifestations are of a hypermetabolic state with increased CO2 production, respiratory acidosis, increased temperature, and increased oxygen demands. If diagnosed late, MH progresses to multi-organ system failure and death. Current data suggest that mortality has improved to less than 5%. The gold standard for ruling out MH is the contracture test. Genetic testing is also available. MH-susceptible individuals should be clearly identified for safe administration of future anesthetics.
Klippel-Feil syndrome (KFS) is characterised by a short webbed neck and
decreased range of neck movement due to fused cervical vertebrae. Several previous
case reports have described the difficulties with airway management associated
with Klippel-Feil syndrome and have advocated the use of fibre-optic
intubation for elective or emergency surgery [1]. However there are no previous
reports of emergency airway management of patients with Kippel-Feil syndrome
outside of the theatre complex. We describe an ‘off the handle’ technique to
facilitate the use of a Macintosh laryngoscope blade in a patient with Klippel-Feil
syndrome.
A 43 year old man with Klippel-Feil Syndrome was admitted to hospital for
treatment of pneumonia. At 2 am he was found unresponsive by nursing staff.
There was no palpable pulse or respiratory effort so cardiopulmonary resuscitation
(CPR) was started.
Due to the severe fixed flexion deformity of the cervical spine, mask ventilation
was difficult despite use of airway adjuncts. Endotracheal intubation was
attempted, whilst CPR was ongoing, but it was not possible to adequately insert
a short-handled laryngoscope. This was because the limited mouth opening and
fixed space between the chin and the anterior chest wall prevented advancement
of the handle towards the patient’s mouth.
Whilst a laryngeal mask was prepared it was noted that the size 3 Macintosh
blade could be fully inserted into the patient’s mouth after detaching the handle.
The handle could then be reattached to the blade in situ. Although manipulation
of the laryngoscope was limited a Cormack and Lehane Grade 3 view of
the larynx was obtained. A gum elastic bougie was then passed into the trachea,
which was then successfully intubated. Spontaneous cardiac circulation was then
restored and the patient was admitted to the intensive care unit.
Discussion
The airway equipment available on cardiac arrest trolleys outside the theatre
setting is limited. Blind nasal intubation and cricothyrotomy were unlikely to be
successful because of the fixed flexion deformity. An i-gel would also have been
difficult to insert. A polio blade was considered but was not available, nor was a
fibre-optic bronchoscope. In this case a laryngeal mask would have been
inserted if the second attempt at intubation had failed.
This case demonstrates the importance of having short-handled laryngoscopes
available outside the theatre environment. Furthermore, insertion of the blade
prior to attachment of the handle should be considered for the management of
patients with fixed flexion deformities of the neck.
Reference
1. Khawaja OM, Reed JT, Shaefi S, Chitilian HV, Sandberg WS. Crisis resource
management of the airway in a patient with Klippel-Feil syndrome,
congenital deafness, and aortic dissection. Anesthesia and Analgesia 2009;
108: 1220–5.
With the increase in need for anesthesia services outside the operating room, nonoperating room personnel are exposed to situations unique to the surgical environment. Malignant hyperthermia (MH) is an inherited genetic disorder that is triggered specifically by drugs and gases used to induce and maintain anesthesia. If left untreated, this disorder can progress into a cascade of events that can ultimately lead to death. The purpose of this review is to provide radiology and imaging personnel with the knowledge to assist anesthesia providers in the diagnosis, evaluation, and treatment of MH.
Background
A malignant hyperthermia (MH) crisis is a potentially fatal complication in anesthesia and intensive care units (ICU). Rapid administration and adequate dosage of dantrolene is the only known effective pharmacological and causal treatment of an MH crisis. International anesthesiology societies recommend an initial dose of 2.0–2.5 mg/kg body weight (BW). The necessary total dosage should be titrated up to 10 mg/kg BW depending on the effectiveness.
Objective
The goal of this study was an analysis of the stocking situation of dantrolene in Germany. A national survey was conducted amongst members of the German Society of Anaesthesia and Intensive Care (DGAI).
Material and methods
A questionnaire consisting of 19 items was posted online to all DGAI members from 2 September to 30 September 2015. The questionnaire dealt with characterization of the participants, the administration of triggering substances in the operating room and in the ICU of the respective hospitals. The main part covered the amount of stocked dantrolene, the place of storage and emergency availability of stocked dantrolene from elsewhere.
Results
The questionnaire was posted online to 12,415 DGAI members with a response rate of 13.5% (n = 1673). The highest response rate was from 259 directors and heads of anesthesiology units representing 28.3%. In total 93,7% of participants use volatile anesthetics and 82,3% use succinylcholine. In the event of an MH-crisis 40.4% of participants have 36 or more vials of dantrolene available within 5 min, 27.4% have only 24 vials and 18.7% only have 12 vials. Of the anesthesiologists in outpatient surgery 70.6% have a dantrolene stock of less than 36 vials. In those cases with insufficient dantrolene stock, 35.5% of hospitals have no agreement with neighboring hospitals. In the ICU setting, 51.8% of responding participants indicated the use of volatile anesthetics, but only 25.7% stock dantrolene in the ICU. For succinylcholine, 77.3% stated using the drug in the ICU, and 26.0% have a dantrolene stock in the ICU.
Conclusion
Almost all anesthesiologists participating in the online survey use volatile anesthethics and/or succinylcholine. Whereas almost all participants have access to dantrolene, more than half of the units have a stock of dantolene, which is less than that recommended by the DGAI. In the case of low dantrolene stock, only 61% of anesthesia departments have access to additional dantrolene within a time frame of 15min . The results of this online survey demonstrate that the stock of dantrolene may be insufficient in some German hospitals and anesthesiology practices.
Procedures in class B ambulatory facilities are performed exclusively with oral or IV sedative-hypnotics and/or analgesics. These facilities typically do not stock dantrolene because no known triggers of malignant hyperthermia (ie, inhaled anesthetics and succinylcholine) are available. This article argues that, in the absence of succinylcholine, the morbidity and mortality from laryngospasm can be significant, indeed, higher than the unlikely scenario of succinylcholine-triggered malignant hyperthermia. The Society for Ambulatory Anesthesia (SAMBA) position statement for the use of succinylcholine for emergency airway management is presented.
Malignant hyperthermia (MH) is a rare life threatening inherited disorder that is triggered by drugs used for general anesthesia in susceptible persons. The symptoms include rapid increase of body temperature and severe muscle contractions. The present study includes 3 cases of MH and highlights the timely identification of symptoms for rescuing the patient. In case I, a 7-year-old male child underwent surgery with ketamine at a dose of 250 mg. After 4 h of operation, the child went through convulsions, high fever and succumbed within a few hours. High fever was not detected in a timely manner, which is one of the main symptoms of MH. In case II, a 12-year-old male child had convulsions and high fever after simple surgery caused by MH. Once confirmed, immediate measures were taken to lower the body temperature and the child was rescued. In case III, a male 57-year-old was admitted to hospital due to paraplegia. The patient underwent more critical conditions once symptoms of MH appeared. Additionally, antidote dantrolene was unavailable in the first and third case; thus, the progression of disease was not alleviated although active symptomatic and supportive treatment were employed.
This Month
Cost of stocking dantrolene for malignant hyperthermia
Key words: cost-benefit analysis, stocking dantrolene sodium, ambulatory surgical facility, ambulatory surgery center, ASC, malignant hyperthermia, MH, transferring MH patient.
Preparing dantrolene for a mock malignant hyperthermia drill
Key words: malignant hyperthermia, MH, mock drill, dantrolene sodium, new suspension.
Covering chest hair
Key words: surgical attire, hair.
Laundering surgical attire in health care–accredited laundry facilities
Key words: surgical attire, laundry facility, health care–accredited laundry.
Malignant hyperthermia (MH) is an uncommon, life-threatening pharmacogenetic disorder of the skeletal muscle. It presents as a hypermetabolic response in susceptible individuals to potent volatile anesthetics with/without depolarizing muscle relaxants; in rare cases, to stress from exertion or heat stress. Susceptibility to malignant hyperthermia (MHS) is inherited as an autosomally dominant trait with variable expression and incomplete penetrance. It is known that the pathophysiology of MH is related to an uncontrolled rise of myoplasmic calcium, which activates biochemical processes resulting in hypermetabolism of the skeletal muscle. In most cases, defects in the ryanodine receptor are responsible for the functional changes of calcium regulation in MH, and more than 300 mutations have been identified in the RYR1 gene, located on chromosome 19q13.1. The classic signs of MH include increase of end-tidal carbon dioxide, tachycardia, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Up to now, muscle contracture test is regarded as the gold standard for the diagnosis of MHS though molecular genetic test is used, on a limited basis so far to diagnose MHS. The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS. This review summarizes the clinically essential and important knowledge of MH, and presents new developments in the field.
This report presents final 2008 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death.
Information reported on death certificates, which is completed by funeral directors, attending physicians, medical examiners, and coroners, is presented in descriptive tabulations. The original records are filed in state registration offices. Statistical information is compiled in a national database through the Vital Statistics Cooperative Program of the Centers for Disease Control and Prevention's National Center for Health Statistics. Causes of death are processed in accordance with the International Classification of Diseases, Tenth Revision.
In 2008, a total of 2,471,984 deaths were reported in the United States. The age-adjusted death rate was 758.3 deaths per 100,000 standard population, a decrease of 0.2 percent from the 2007 rate and a record low figure. Life expectancy at birth rose 0.2 years, from 77.9 years in 2007 to a record high 78.1 years in 2008. The age-specific death rate increased for age group 85 years and over. Age-specific death rates decreased for age groups: less than 1 year, 5-14, 15-24, 25-34, 35-44, and 65-74 years. The age-specific death rates remained unchanged for age groups: 1-4, 45-54, 55-64, and 75-84 years. The 15 leading causes of death in 2008 remained the same as in 2007, but Chronic lower respiratory diseases and suicide increased in the ranking while stroke and septicemia decreased in the ranking. Stroke is the fourth leading cause of death in 2008 after more than five decades at number three in the ranking. Chronic lower respiratory diseases is the third leading cause of death for 2008. The infant mortality rate decreased 2.1 percent to a historically low value of 6.61 deaths per 1000 live births in 2008.
The decline of the age-adjusted death rate to a record low value for the United States and the increase in life expectancy to a record high value of 78.1 years are consistent with long-term trends in mortality.
Clinical problem:
Volatile anesthetics and/or succinylcholine may trigger a potentially lethal malignant hyperthermia (MH) event requiring critical care crisis management. If the MH triggering anesthetic is given in an ambulatory surgical center (ASC), then the patient will need to be transferred to a receiving hospital. Before May 2010, there was no clinical guide regarding the development of a specific transfer plan for MH patients in an ASC. MECHANISM BY WHICH THE STATEMENT WAS GENERATED: A consensual process lasting 18 months among 13 representatives of the Malignant Hyperthermia Association of the United States, the Ambulatory Surgery Foundation, the Society for Ambulatory Anesthesia, the Society for Academic Emergency Medicine, and the National Association of Emergency Medical Technicians led to the creation of this guide. EVIDENCE FOR THE STATEMENT: Most of the guide is based on the clinical experience and scientific expertise of the 13 representatives. The list of representatives appears in Appendix 1. The recommendation that IV dantrolene should be initiated pending transfer is also supported by clinical research demonstrating that the likelihood of significant MH complications doubles for every 30-minute delay in dantrolene administration (Anesth Analg 2010;110:498-507).
Statement:
This guide includes a list of potential clinical problems and therapeutic interventions to assist each ASC in the development of its own unique MH transfer plan. Points to consider include receiving health care facility capabilities, indicators of patient stability and necessary report data, transport team considerations and capabilities, implementation of transfer decisions, and coordination of communication among the ASC, the receiving hospital, and the transport team. See Appendix 2 for the guide.
This report presents national estimates of surgical and nonsurgical procedures performed on an ambulatory basis in hospitals and freestanding ambulatory surgery centers in the United States during 2006. Data are presented by types of facilities, age and sex of the patients, and geographic regions. Major categories of procedures and diagnoses are shown by age and sex. Selected estimates are compared between 1996 and 2006.
The estimates are based on data collected through the 2006 National Survey of Ambulatory Surgery by the Centers for Disease Control and Prevention's National Center for Health Statistics (NCHS). The survey was conducted from 1994-1996 and again in 2006. Diagnoses and procedures presented are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM).
In 2006, an estimated 57.1 million surgical and nonsurgical procedures were performed during 34.7 million ambulatory surgery visits. Of the 34.7 million visits, 19.9 million occurred in hospitals and 14.9 million occurred in freestanding ambulatory surgery centers. The rate of visits to freestanding ambulatory surgery centers increased about 300 percent from 1996 to 2006, whereas the rate of visits to hospital-based surgery centers remained largely unchanged during that time period. Females had significantly more ambulatory surgery visits (20.0 million) than males (14.7 million), and a significantly higher rate of visits (132.0 per 1000 population) compared with males (100.4 per 1000 population). Average times for surgical visits were higher for ambulatory surgery visits to hospital-based ambulatory surgery centers than for visits to freestanding ambulatory surgery centers for the amount of time spent in the operating room (61.7 minutes compared with 43.2 minutes), the amount of time spent in surgery (34.2 minutes compared with 25.1 minutes), the amount of time spent in the postoperative recovery room (79.0 minutes compared with 53.1 minutes), and overall time (146.6 minutes compared with 97.7 minutes). Although the majority of visits had only one or two procedures performed (56.3 percent and 28.5 percent, respectively), 2.6 percent had five or more procedures performed. Frequently performed procedures on ambulatory surgery patients included endoscopy of large intestine (5.8 million), endoscopy of small intestine (3.5 million), extraction of lens (3.1 million), injection of agent into spinal canal (2.7 million), and insertion of prosthetic lens (2.6 million). The leading diagnoses at ambulatory surgery visits included cataract (3.0 million); benign neoplasms (2.0 million), malignant neoplasms (1.2 million), diseases of the esophagus (1.1 million), and diverticula of the intestine (1.1 million).
AN ARTICLE in the February 2000 issue of JAMA concluded that annual retinal screening for many individuals with type 2 diabetes mellitus may not be warranted on grounds of cost-effectiveness. Vijan et al1 reported that, compared with biannual screening, annual retinopathy screening for low-risk patients with diabetes costs more than $100 000 for each additional quality-adjusted life year (QALY) gained. The results of a study published in the March 2000 issue of the New England Journal of Medicine concluded that extending hospital stays beyond 4 days for patients with uncomplicated myocardial infarctions was economically unattractive, costing more than $105 000 per QALY gained.2 These studies demonstrate that commonly used interventions may not be worthwhile investments of health care resources. By contrast, a study published in the June 2000 issue of the Annals of Internal Medicine concluded that, compared with no treatment, sildenafil (Viagra) is a cost-effective treatment for erectile dysfunction, producing an incremental QALY for the relatively low cost of $11 000.3 The latter study raises questions about whether many health care insurers were hasty in deciding that they would not add sildenafil to the list of services covered by their health plans.4
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000-100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%.
: Malignant hyperthermia (MH) is triggered by many anesthetics. This study investigates the epidemiology of MH, its association with various drugs, and mortality rates. Five hundred three cases of MH were reported. MH patients were demographically similar worldwide. Pediatric (52.1%, age <15 yr) and male (65.8%) MH patients exceed the general surgical population. Congenital defects and musculoskeletal surgical procedures were associated clearly with MH. Previous uneventful anesthesia (20.9%) and absence of positive family history (75.9%) were common. Case fatality rates have decreased with time to 10% since 1985. This decline is partly and independently due to dantrolene therapy, as well as to better vigilance and awareness on the part of the anesthetic community. (Anesth Analg 1993;77:297-304)
Case reports have linked malignant hyperthermia (MH) to several genetic diseases.
The objective of this study was to quantitatively assess excess comorbidities associated with MH diagnosis in pediatric hospital discharge records.
Data for this study came from the Kids' Inpatient Database (KID) for the years 2000, 2003, and 2006. The KID contains an 80% random sample of patients under the age of 21 discharged from short-term, non-Federal hospitals in the United States, with up to 19 diagnoses recorded for each patient. Using all pediatric inpatients as the reference, we calculated the standardized morbidity ratios (SMRs) and 95% confidence intervals (CIs) for children with MH diagnosis according to major disease groups and specific medical conditions.
Of the 5,916,989 nonbirth-related hospital discharges studied, 175 had a recorded diagnosis of MH. Compared with the general pediatric inpatient population, children with MH diagnosis were significantly more likely to be diagnosed with diseases of the musculoskeletal system and connective tissue (SMR 5.7; 95% CI: 3.9-7.9), diseases of the circulatory system (SMR 3.3; 95% CI: 2.1-4.8), and congenital anomalies (SMR 3.2; 95% CI: 2.3-4.4). The specific diagnosis that was most strongly associated with MH was muscular dystrophies (SMR 31.3; 95% CI 12.6-64.6).
Diseases of the musculoskeletal system and connective tissue are significantly associated with MH diagnosis in children. Further research is warranted to determine the clinical utility of these comorbidities in assessing MH susceptibility in children.
For many years experimental observations have raised questions about the rationality of economic agents--for example, the Allais Paradox or the Equity Premium Puzzle. The problem is a narrow notion of rationality that disregards fear. This article extends the notion of rationality with new axioms of choice under uncertainty and the decision criteria they imply (Chichilnisky, G., 1996a. An axiomatic approach to sustainable development. Social Choice andWelfare 13, 257-321; Chichilnisky, G., 2000. An axiomatic approach to choice under uncertainty with Catastrophic risks. Resource and Energy Economics; Chichilnisky, G., 2002. Catastrophical Risk. Encyclopedia of Environmetrics, vol. 1. John Wiley & Sons, Ltd., Chicester). In the absence of catastrophes, the old and the new approach coincide, and both lead to standard expected utility. A sharp difference emerges when facing rare events with important consequences, or catastrophes. Theorem 1 establishes that a classic axiom of choice under uncertainty - Arrow's Monotone Continuity axiom, or its relatives introduced by DeGroot, Villegas, Hernstein and Milnor - postulate rational behavior that is [`]insensitive' to rare events as defined in (Chichilnisky, G., 1996a. An axiomatic approach to sustainable development. Social Choice andWelfare 13, 257-321; Chichilnisky, G., 2000. An axiomatic approach to choice under uncertainty with Catastrophic risks. Resource and Energy Economics; Chichilnisky, G., 2002. Catastrophical Risk. Encyclopedia of Environmetrics, vol. 1. John Wiley & Sons, Ltd., Chicester). Theorem 2 replaces this axiom with another that allows extreme responses to extreme events, and characterizes the implied decision criteria as a combination of expected utility with extremal responses. Theorems 1 and 2 offer a new understanding of rationality consistent with previously unexplained observations about decisions involving rare and catastrophic events, decisions involving fear, the Equity Premium Puzzle, [`]jump di
Our research addresses fundamental long-standing concerns in the compensating wage differentials literature and its public policy implications: the econometric properties of estimates of the value of statistical life (VSL) and the wide range of such estimates from about $0 to almost $30 million. Here we address most of the prominent econometric issues by applying panel data, a new and more accurate fatality risk measure, and systematic application of panel data estimators. Controlling for measurement error, endogeneity, latent individual heterogeneity that may be correlated with the regressors, state dependence, and sample composition yields an estimated value of a statistical life of about $7 million–$12 million, which we show can clarify greatly the cost-effectiveness of regulatory decisions. We show that probably the most important econometric issue is controlling for latent heterogeneity; less important is how one does it.
Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disorder with an estimated mortality of less than 5%. The purpose of this study was to evaluate the current incidence of MH and the predictors associated with in-hospital mortality in the United States.
The Nationwide Inpatient Sample, which is the largest all-payer inpatient database in the United States, was used to identify patients discharged with a diagnosis of MH during the years 2000-2005. The weighted exact Cochrane-Armitage test and multivariate logistic regression analyses were used to assess trends in the incidence and risk-adjusted mortality from MH, taking into account the complex survey design.
From 2000 to 2005, the number of cases of MH increased from 372 to 521 per year. The occurrence of MH increased from 10.2 to 13.3 patients per million hospital discharges (P = 0.001). Mortality rates from MH ranged from 6.5% in 2005 to 16.9% in 2001 (P < 0.0001). The median age of patients with MH was 39 (interquartile range, 23-54 yr). Only 17.8% of the patients were children, who had lower mortality than adults (0.7% vs. 14.1%, P < 0.0001). Logistic regression analyses revealed that risk-adjusted in-hospital mortality was associated with increasing age, female sex, comorbidity burden, source of admission to hospital, and geographic region of the United States.
The incidence of MH in the United States has increased in recent years. The in-hospital mortality from MH remains elevated and higher than previously reported. The results of this study should enable the identification of areas requiring increased focus in MH-related education.
Questionnaires were sent to all anesthesia departments in Denmark to determine the total number of anesthetics given per year, and the distribution of different types of anesthesia. All cases of suspected malignant hyperthermia forwarded to the Danish Malignant Hyperthermia Register during a 6.5 yr period were reviewed and divided into subgroups according to clinical criteria. The incidence of suspected malignant hyperthermia in these subgroups was calculated in relation to type of anesthesia. The results are based on information about 386,250 anesthetics and 154 cases of suspected malignant hyperthermia. All cases of malignant hyperthermia occurred during general anesthesia, and more than 75% during anesthesia with a combination of potent inhalation agents and succinylcholine. The incidence of fulminant malignant hyperthermia was low: 1 in 250,000 total anesthetic procedures, but 1 in 62,000 anesthetic procedures with a combination of potent inhalation agents and succinylcholine. Masseter spasm occurred in 1 of 12,000 anesthetic procedures in which succinylcholine was administered. Suspicion of malignant hyperthermia was raised in 1 of 16,000 anesthetics total, but in 1 of 4,200 anesthetics with the above-mentioned combination of agents.
Information was collected on 89 patients who responded to general anaesthetics with malignant hyperthermia. The syndrome occurred at the rate of about one in 14,000 anaesthetics among a hospital population of children. The patient mortality was 64 per cent. The finding that males were somewhat more commonly affected than were females does not contradict previous observations of dominant inheritance of the syndrome. About one-third of patients had relatives who were also affected with malignant hyperthermia, although a few patients had had previous uneventful general anaesthetics. The racial origin was varied. A pre-existing muscle or musculoskeletal disease was present more frequently than expected in patients who manifested rigidity.
Clinical manifestations followed the administration of a muscle relaxant or a potent inhalational agent, usually halothane. Fever was invariably present within the first one to two hours of the induction. Skeletal muscle rigidity occurred in more than two-thirds of cases. The use of anticholinergic drugs given preoperatively appeared to increase the incidence of rigidity. The use of non-depolarizing relaxants in vain attempts to overcome the rigidity has certainly not improved the chances of survival. The higher the absolute maximum temperature and the longer the duration of anaesthesia, the greater was the mortality rate.
It is possible that the cases with and without rigidity represent slightly different disorders. In cases characterized by rigidity there were often tachypnoea, tachycardia, arrhythmias, acute heart failure, late neurological deterioration, hypoxia, respiratory and metabolic acidoses, hyperkalaemia, hypocalcaemia, elevated serum enzymes, impaired blood coagulation, haemo- and myoglobinuria, oliguria, and muscle biopsy abnormalities.
Treatment included a wide variety of therapeutic measures. No particular agent could be credited with having improved the survival rate. So far, the most effective treatment was early detection and early cessation of anaesthesia.
Anesthesiologists from 65 institutions participated in a multicenter study to assess the efficacy of lyophilized intravenous dantrolene sodium in treating anesthetically related malignant hyperthermia (MH). Of 21 patients treated with the drug, eight were judged to have unequivocal MH and were treated according to study protocol. Three were judged to have probable MH and were also treated according to study protocol. All 11 recovered without sequelae from MH and without adverse drug effects. A mean dantrolene dose of 2.5 mg/kg in these patients produced significant changes in clinical and biochemical parameters suggestive of decreased cellular metabolism. Four patients with unequivocal MH were treated with intravenous dantrolene more than 24 h after the diagnosis of MH; this delay in treatment of clinical signs in these patients, the mortality rate was 75 per cent, which is comparable to that reported without dantrolene. The six remaining patients had episodes of questionable MH during or subsequent to anesthesia and were treated with dantrolene. There was insufficient evidence to justify an unequivocal or probable diagnosis of MH, and they, therefore, were not included in the study. All survived and had no adverse drug reactions. Dantrolene therapy resulted in a statistically significantly lower mortality rate than would be expected in MH patients. The study supports animal data suggesting that dantrolene is specific in reversing MH.
Malignant hyperthermia (MH) is triggered by many anesthetics. This study investigates the epidemiology of MH, its association with various drugs, and mortality rates. Five hundred three cases of MH were reported. MH patients were demographically similar worldwide. Pediatric (52.1%, age < 15 yr) and male (65.8%) MH patients exceed the general surgical population. Congenital defects and musculoskeletal surgical procedures were associated clearly with MH. Previous uneventful anesthesia (20.9%) and absence of positive family history (75.9%) were common. Case fatality rates have decreased with time to 10% since 1985. This decline is partly and independently due to dantrolene therapy, as well as to better vigilance and awareness on the part of the anesthetic community.
We investigated the transition of clinical signs of fulminant-type malignant hyperthermia (f-MH) by analyzing a database consisting of 383 cumulative cases of f-MH from 1961 to 2004. The cases were divided by time period into group 1 (1961-1984), group 2 (1985-1994), and group 3 (1995-2004). The variables considered were age, sex, type of agents used (succinylcholine and volatile anesthetics), dantrolene administration, clinical signs, laboratory data, and mortality. The level of statistical significance was considered to be less than 5%. Groups 1, 2, and 3 consisted of 196, 127, and 60 cases, respectively. In groups 1, 2, and 3, the rates of dantrolene administration were 18.4%, 93.6%, and 86.7%; the rates of occurrence of ventricular arrhythmia were: 75.2%, 55.6%, and 35.0%; and the rates of generalized muscle rigidity were 64.7%, 60.9%, and 23.9%, respectively. The mortality rate decreased over time, from 42.3% in group 1, to 15.0% in group 2 and group 3. We considered that this decrease occurred because of the increased use of dantrolene and the early diagnosis of malignant hyperthermia in the latter two groups.
The authors determined associated cardiac arrest and death rates in cases from Canada and the United States as reported to The North American Malignant Hyperthermia (MH) Registry and analyzed factors associated with a higher risk of poor outcomes.
The authors searched the database for AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports with inclusion criteria as follows: event date between January 1, 1987, and December 31, 2006; "very likely" or "almost certain" MH as ranked by MH Clinical Grading Scale; location in Canada or the United States; and one or more anesthetic agents given. The exclusion criterion was a pathologic condition other than MH independently judged by the authors. Severe MH outcomes were analyzed as regards clinical history and presentation, using Wilcoxon rank sum tests for continuous variables and Pearson exact chi-square tests for categorical variables. A Bonferroni correction adjusted for multiple comparisons.
Of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2-31 yr). Associated factors were muscular build (odds ratio, 18.7; P = 0.0016) and disseminated intravascular coagulation (odds ratio, 49.7; P < 0.0001). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide (216 vs. 87 min; P = 0.003). Unrelated factors included patient or family history, anesthetic management, and the MH episode.
Modern US anesthetic practice did not prevent MH-associated cardiac arrest and death in predominantly young, healthy patients undergoing low- to intermediate-risk surgical procedures.
Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.
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