Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain.

BACKGROUND: Neuromuscular blocking (NMB) agents are often administered to facilitate tracheal intubation and prevent patient movement during surgical procedures requiring the use of general anesthetics. Incomplete reversal of NMB, can lead to residual NMB, which can increase the risk of post-operative pulmonary complications. Sugammadex is indicated to reverse neuromuscular blockade induced by rocuronium or vecuronium in adults. The aim of this study is to estimate the clinical and economic impact of introducing sugammadex to routine reversal of neuromuscular blockade (NMB) with rocuronium in Spain. METHODS: A decision analytic model was constructed reflecting a set of procedures using rocuronium that resulted in moderate or deep NMB at the end of the procedure. Two scenarios were considered for 537,931 procedures using NMB agents in Spain in 2015: a scenario without sugammadex versus a scenario with sugammadex. Comparators included neostigmine (plus glycopyrrolate) and no reversal agent. The total costs for the healthcare system were estimated from the net of costs of reversal agents and overall cost offsets via reduction in postoperative pneumonias and atelectasis for which incidence rates were based on a Spanish real-world evidence (RWE) study. The model time horizon was assumed to be one year. Costs were expressed in 2019 euros (€) and estimated from the perspective of a healthcare system. One-way sensitivity analysis was carried out by varying each parameter included in the model within a range of +/- 50%. RESULTS: The estimated budget impact of the introduction of sugammadex to the routine reversal of neuromuscular blockade in Spanish hospitals was a net saving of €57.1 million annually. An increase in drug acquisition costs was offset by savings in post-operative pulmonary events, including 4806 post-operative pneumonias and 13,996 cases of atelectasis. The total cost of complications avoided was €70.4 million. All parameters included in the model were tested in sensitivity analysis and were favorable to the scenario with sugammadex. CONCLUSIONS: This economic analysis shows that sugammadex can potentially lead to cost savings for the reversal of rocuronium-induced moderate or profound NMB compared to no reversal and reversal with neostigmine in the Spanish health care setting. The economic model was based on data obtained from Spain and from assumptions from clinical practice and may not be valid for other countries.

[Evaluation of muscle relaxant requirement for hospital anesthesia].

The rationale for cost-effectiveness of modern muscle relaxants (MR) administration in general anesthesia was evaluated. New MRs are more expensive than traditionally used pipecuronium and succinylcholine. However, the old MRs are often required as a block reversion with anticholinesterase medicines at the end of surgery, the longer artificial lung ventilation and observation in patients during recovery in intensive care unit. It was found that the district military hospital had done an annual average of about 900 general anesthesia assisted with artificial ventilation and muscle relaxation. About 2% of all anesthesias accrue to short-term anesthesia, the 27% to medium-term and 71% to long-term. 81% of the medium-term anesthesia accrue small hospitals. According to cost/effectiveness the most optimal muscle relaxants administration scheme for short-term (up to 30 min) anesthesia was mivacurium, for the operation of medium duration (30-120 min)--rocuronium, for long-term (120 min)--pipecuronium. An electronic form of annual report, which allows to obtain the necessary data for calculation of annual muscle relaxants demand and costs both in hospital and in the whole of the armed forces quickly, was developed.

Cost analysis and safety comparison of Cisatracurium and Atracurium in patients undergoing general anesthesia.

BACKGROUND: Non-depolarizing neuromuscular blocking agents (NMB) differ in pharmacokinetic and pharmacodynamic parameters. An anesthesiologist according to these similarities and differences is able to choose the least costly one if the same safety profile and same clinical benefit achieved with the different alternatives. AIM: The main objective of this study is to evaluate the economic and adverse drug reactions prevalence and differences between cisatracurium and atracurium the two non-depolarizing NMB drugs, which are widely used in adult patients undergoing surgery with general anesthesia in a teaching Hospital in Iran. MATERIALS AND METHODS: A cost analysis and adverse drug reactions (ADR) monitoring were performed. Only direct costs were considered and data were collected through a prospective randomized study. Regardless of the type of surgery, 100 patients were randomly divided into two equal groups to receive either cisatracurium or atracurium by anesthesiologists. ADRs prevalence and cost differences between patients receiving one of the two non-depolarizing NMB agents were evaluated by independent sample t-test and Chi-square test respectively. RESULTS: No significant difference was observed between the two groups of patients in demographic data. There was no statistical difference in the ADR prevalence in both groups. The numbers of ADR within atracurium group was higher than cisatracurium group, but this distinction was not statistically significant (p > 0.05). It was significant difference in cost between the two neuromuscular blocking drugs (p < 0.05). CONCLUSIONS: According to our study it seems that atracurium and cisatracurium had similar safety profile and atracurium had a cost benefit relative to cisatracurium in initial loading doses. In patients with instability in hemodynamic parameters the cisatracurium was the appropriate choice.  

[To reduce drug expenditure in the operating room (OR)--a paradigm].

BACKGROUND: The main advantages of pharmacy controlled IV preparations (CIVAS) are reduced expenditures, contaminations, and human errors. Today, IV preparations by physicians in the operating room (OR) are based on axioms such as: purchased drugs have standard dosages, IV are prepared immediately before operation, quantity of drug used is unpredictable due to patient's body weight and type of operation and opened injections can't be used for different patients and operations. Due to those limitations, the quantities of drugs used are significantly lower than supplied and wastage cost is high. AIM: To optimize CIVAS and reduce drug expenditure, using techniques from management and engineering sciences. METHOD: A model of optimization, based on credibility and prediction tests was used to analyze CIVAS. The model uses parameters such as number and type of operations, drugs and quantities/operation. It identifies wastage for each drug used (quantities and cost) and predicts optimal doses and quantities to be prepared. RESULTS: Although wastage (quantities) ranged from 30-70%, wastage cost was attributed mainly to two drugs: rocuronium (72%) and propofol (13 %). The model predicts that preparation of three standard doses of rocuronium will allow a 52.7% cost saving from the OR's IV drug budget. CONCLUSION: This optimization model can be applied in wards where wastage cost of IV drugs is high. It will indicate which standard doses of which drug should be prepared, that will enable lowest wastage with minimal addition of manpower.

Similar preoperative hemodynamic response to pancuronium and rocuronium in high-risk cardiac surgical patients.

AIM: Rocuronium may be a good alternative to pancuronium in cardiac surgical patients. We evaluate the hemodynamic response to rocuronium and pancuronium administered to cardiac surgical patients. METHODS: A single-blind, randomized clinical trial was carried out at the National Institute of Cardiology in Mexico. Twenty-two patients older than 18 years, NYHA class III-IV, and scheduled to undergo an elective cardiovascular surgical procedure were enrolled. Patients were randomly allocated to receive an i.v. bolus dose of either pancuronium 100 microg/kg or rocuronium 600 microg/kg. Peripheral arterial (radial) and venous cannulations and insertion of a multi-lumen pulmonary artery flotation catheter through the right internal jugular vein were carried out under local anesthesia. Anesthetic induction with an i.v. bolus dose of fentanyl 700 microg and diazepam 20 mg was performed and thereafter the neuromuscular blocking agent was administered. Ventilation with O2 100% was performed until a TOF < or =5% was observed and tracheal intubation was performed. After intubation, patients were maintained with O2 10 mL/kg administered by means of a pulmonary ventilator at a pressure of 20-25 cm H2O. The basal, pre-laryngoscopy, post-intubation, and pre-operative recording of a set of cardiovascular parameters were obtained. RESULTS: No differences (P>0.05) in the hemodynamic response were observed between pancuronium and rocuronium nor during the different evaluation times in each group. CONCLUSIONS: Rocuronium can be a safe alternative to pancuronium for patients requiring cardiac surgical procedures.

[Frequency distribution of dibucaine numbers in 24,830 patients]. / Verteilungsmuster der Dibucainzahl bei 24.830 Patientinnen und Patienten.

PURPOSE: Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. METHODS: Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. RESULTS: A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. CONCLUSIONS: An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.

Equi-lasting doses of rocuronium, compared to mivacurium, result in improved neuromuscular blockade in patients undergoing gynecological laparoscopy : [Des doses de durée équivalente de rocuronium, comparé au mivacurium, améliorent la curarisation chez des patientes qui subissent une laparoscopie gynécologique].

PURPOSE: To compare equi-lasting doses of a short-acting (mivacurium) to an intermediate-acting (rocuronium) neuromuscular relaxant, with regard to intubating conditions, efficacy, number of maintenance doses, hemodynamic alterations, adverse events and costs, in patients undergoing laparoscopic gynecological surgery. METHODS: Sixty patients were randomly allocated to receive either 0.2 mg*kg(-1) (3 x ED(95)) mivacurium or 0.5 mg*kg(-1) (1.7 x ED(95)) rocuronium, under propofol/fentanyl anesthesia. T1, first twitch of the train-of-four (TOF) and TOF ratio (T4:T1) were used to evaluate neuromuscular block using the Relaxometer(R) mechanomyograph. The trachea was intubated when T1 was maximally suppressed. Neuromuscular block was maintained at 25% T1 with equi-lasting doses of 0.075 mg*kg(-1) mivacurium or 0.15 mg*kg(-1) rocuronium. RESULTS: Mean (min) +/- SD mivacurium onset time (1.9 +/- 0.4) was longer than that of rocuronium (1.3 +/- 0.3). This did not yield a statistical difference in intubating conditions between the two groups. Interval 25-75% T1 recovery and time to 0.8 TOF recovery were prolonged following rocuronium (11.9 +/- 3.9, 52.6 +/- 15.5 respectively) compared to mivacurium (6.7 +/- 2.3, 39.2 +/- 8.1 respectively). More patients, 22/30, required mivacurium maintenance doses compared to 14/30 patients in the rocuronium group. Arterial blood pressure declined and 13/30 patients manifested erythema following mivacurium administration. The acquisition costs of rocuronium (6.93 Euro/patient) were 23% lower compared to mivacurium (8.96 Euro/patient). CONCLUSION: Equi-lasting doses of rocuronium resulted in favourable intubating conditions more rapidly, improved hemodynamic stability, required less frequent administration of maintenance doses and were not associated with erythema, compared to mivacurium.

Cost analysis of neuromuscular blocking agents in the operating room: cisatracurium, atracurium, vecuronium and rocuronium.

Cisatracurium (C), Atracurium (A), Rocuronium (R) and Vecuronium (V) are four neuromuscular blockers (NMB) used in the operating room with similar efficacy, defined as adequate muscle relaxation, but different pharmacokinetics. C and A have organ-independent elimination, A is associated with histamine release and R has a shorter onset time. The objective of this study was to economically compare these four NMB from the hospital point of view in order to facilitate drug selection. A cost analysis was performed. Only direct costs were considered and data were collected through a retrospective chart review. A total of 151 patient charts were randomly selected. Differences between patients receiving one of the four NMB were evaluated by ANOVA or Kruskal-Wallis tests. Then a multiple linear regression analysis was conducted. In the chart review, no significant difference was observed between the four groups of patients in age, weight or surgery duration (p > 0.05). Multiple regression analysis revealed that atracurium was on average PTA 237 (1 Euro = PTA 166) cheaper per surgery than any other NMB after adjusting for other factors (p < 0.01) and there is no significant difference in cost between the other three NMBs (p > 0.1). We recommend the use of rocuronium when a quick onset is needed and the patient does not have hepatic failure, cisatracurium when a haemodynamic instability is possible and atracurium in the remaining cases. If just one NMB can be included in the drug formulary we would select cisatracurium due to its pharmacological advantages over atracurium with a small increment in cost.

Drug use inefficiency: a hidden source of wasted health care dollars.

UNLABELLED: A potential area for departmental savings is to minimize inefficient use of pharmaceuticals. We recorded drug waste data for multiple drugs for a fiscal year and surveyed providers' knowledge of departmental drug waste. Six large-cost or large-volume use drugs were chosen for study: thiopental, succinylcholine, rocuronium, atracurium, midazolam, and propofol. Amounts administered to patients were collected for one year by using a computerized anesthesia record keeper. Total drug distributed was the number of vials restocked by pharmacy for the year. An efficiency index, the percent administered to patients, was calculated for each drug. Drug administration to 25,481 patients was analyzed. Drug use efficiency indices were: atracurium 29%; thiopental, 31%; succinylcholine, 33%; propofol, 49%; midazolam, 53%; rocuronium, 61%. The total cost of unadministered study drugs was $165,667, 26% of the expenditure for all drugs. Most dollars wasted were for propofol, $80,863, and thiopental, $32,839. The reason most cited for drug waste was the disposal of full, or partially full, syringes. Drug wastage represents a significant portion of the entire anesthesia drug budget. Waste reduction strategies should allow a portion of the "avoidable" waste to be reduced. IMPLICATIONS: Unadministered drug amounts were measured for six study drugs over one fiscal year and found to be significant; the cost of unadministered drugs totaled $165,667. The reason most cited for waste was disposal of full, or partially full, syringes.

Mivacurium or vecuronium for paediatric ENT surgery. Clinical experience and cost analysis.

BACKGROUND: The present study compared the quality of neuromuscular block and costs after equipotent doses of mivacurium and vecuronium in the context of paediatric ENT surgery. METHODS: A total of 30 children undergoing elective tonsillectomy were included and randomised in two groups (n = 15 for each) according to the neuromuscular blocking agent (NMBA) used. Anaesthesia was induced with alfentanil (15 micrograms/kg), propofol (3 mg/kg) and either 0.2 mg/kg mivacurium or 0.14 mg/kg vecuronium. For maintenance of anaesthesia propofol (8-12 mg/kg/h) was given. Neuromuscular block was assessed by electromyography using train-of four stimulation and the following parameters were quantified: Twitch height (T1) 2 min after the initial bolus of the myorelaxant; duration until recovery to 10% T1, number and duration of bolus injections of the myorelaxant needed to maintain neuromuscular block to a T1 < 10%. In addition, the intubating conditions, number of patients needing pharmacological reversal at the end of surgery, adverse reactions and the costs for neuromuscular block and pharmacological antagonization were assessed. RESULTS: Intubation conditions were comparable between both study groups: mivacurium--excellent: 7, good: 5, not acceptable: 1; vecuronium--excellent: 11, good: 4 (n.s.). T1 at 2 min was 16 (15)% for mivacurium and 6 (9)% for vecuronium (P < 0.05). Time to 10% T1 recovery was 6.1 (1.7) min for mivacurium and 21.8 (3.7) min for vecuronium (P < 0.01). In the mivacurium group 7 repetitive doses (range: 4-18) were needed to maintain T1 < 10% during surgery, whereas children treated with vecuronium needed only 1 maintenance dose (range: 0-2) (P < 0.01). Two children in the mivacurium group and 11 in the vecuronium group required pharmacological reversal of the NMB at the end of surgery (P < 0.01). The overall costs of NMB were significantly higher in the mivacurium group as compared to vecuronium 12.88 (4.5) Euro vs 9.96 (2.4) Euro; P < 0.05. CONCLUSIONS: In conclusion, mivacurium-induced NMB is of very short duration in paediatric patients, and therefore repetitive doses are required to maintain a deep neuromuscular block. Nevertheless, residual paralysis is less frequent after mivacurium. The neuromuscular block after mivacurium was more expensive and residual paralysis less frequent compared to vecuronium.

Economic aspects of different muscle relaxant regimens.

OBJECTIVE: At a time of cost reduction in medical care efforts to manage the ever-increasing costs of new pharmaceutical drugs become increasingly important. Costs of four different muscle relaxant regimens including the new intermediate-acting neuromuscular blocking drugs (NMBD) cisatracurium and rocuronium will be analyzed. METHODS: Eighty patients undergoing laparoscopic cholecystectomy were prospectively studied. All patients received standardized general anaesthesia with desflurane/fentanyl. Muscle relaxation was achieved with atracurium, cisatracurium, vecuronium, or rocuronium with 20 patients in each group. Intraoperatively muscle relaxants were added to maintain two twitches of the train-of-four (TOF) assessment. RESULTS: There were no differences among the four groups regarding biometric data, duration of surgery and anesthesia, number of patients with reversal of neuromuscular blockade, and time of extubation. Length of stay in the postanesthesia care unit (PACU) and the incidence of side effects were similar in all groups. Total costs of used drugs were significantly lowest in the atracurium-treated patients (per patient: 18.27 Euro) and significantly highest in the cisatracurium group (26.71 Euro) compared with the other groups (vecuronium: 22.61 Euro; rocuronium: 22.63 Euro). CONCLUSION: It is summarized that the use of cisatracurium was associated with higher costs compared to a standard muscle relaxant regimen using atracurium, whereas patient outcome was the same in all study groups. The routine use of the newer NMBDs can only be justified economically, if considerable improvements to clinical practice can be demonstrated.

The costs of intense neuromuscular block for anesthesia during endolaryngeal procedures due to waiting time.

UNLABELLED: The goal of this double-blinded, prospective study was to compare the costs incurred by waiting time of intense neuromuscular block while posttetanic count (PTC) was maintained at 0-2 during jet ventilation. Fifty patients were randomized into five groups to receive atracurium (ATR), mivacurium (MIV), rocuronium (ROC), vecuronium (VEC), and succinylcholine (SUCC). PTC < or =2 was maintained until completion of laryngomicroscopy by administering additional doses of relaxants or by adjusting the speed of the infusion of SUCC. We compared waiting time, i.e., onset time and recovery time, and costs of intense neuromuscular block. The expenses due to waiting time were calculated based on the average costs in the otorhinolaryngological operating room in Tampere University Hospital: FIM 40 (approximately $8) per minute in 1997. MIV and SUCC differ favorably from ATR, ROC, and VEC when waiting time and costs are concerned. The recovery times with MIV and SUCC were considerably shorter than those with ATR, ROC, and VEC (P < 0.001 in all pairwise comparisons). Using the muscle relaxant with the longest waiting time instead of that with the shortest waiting time (difference 21.8 min) cost more than FIM 800 (approximately $160) extra per patient. IMPLICATIONS: In this randomized, double-blinded, prospective study, we evaluated the costs of intense neuromuscular block due to waiting time. Succinylcholine and mivacurium are the most economical muscle relaxants to use when intense neuromuscular block is mandatory. Using intermediate-acting muscle relaxants results in unduly prolonged recovery time and extra costs.

Combinación de relajantes musculares no despolarizantes: sinergismo de potenciación farmacológica / Combination of nondepolarizing muscle relaxants: synergism of potentiation

Introducción: El empleo de ciertas asociaciones de relajantes musculares no despolarizantes a dosis subterapéuticas, aprovechando su sinergismo de potenciación, es una alternativa útil para la práctica anestesiológica diaria. Objetivos: 1.- Desarrollar las bases farmacológicas del fenómeno sinérgico, 2.- comentar los modelos experimentales y el análisis estadístico que lo avalan, 3.- enumerar las ventajas clínicas de su empleo y 4.- revisar y poner al día la bibliografía sobre el tema. Discusión: Desde las primeras observaciones en 1969, con la mezcla d-tubocurarina-gallamina, hasta la actualidad, con la asociación de los nuevos relajantes musculares no despolarizantes (atracurio-vecuronio, mivacurio-rocuronio, cisatracurio-rocuronio, etc.), este fenómeno de potenciación ha demostrado ofrecer ventajas tanto en el campo de la farmacología clínica como en el de la farmacoeconomía. Entre los mecanismos de potenciación propuestos, los más aceptados son los relacionados con la particular estructura del receptor nicotínico y con la combinación de mecanismos pre y postsinápticos en la unión neuromuscular. La comprobación experimental se acompaña de la determinación de las curvas dosis-respuesta, los gráficos de interacción y los análisis isobolográfico y algebraico. Las ventajas clínicas del fenómeno estudiado son: 1.- empleo de dosis subterapéuticas, con mayor margen de seguridad para los efectos cardiovasculares, 2.- menor tiempo de latencia, 3.- duración clínica y tiempos de recobro generalmente más breves que con los componentes aislados, 4.- adecuado grado de bloqueo neuromuscular, 5.- predictibilidad para los tiempos de administración y recuperación, 6.- fácil reversión con neotigmina y 7.- menor costo. Conclusiones: El uso de combinaciones de relajantes musculares no despolarizantes, en virtud del sinergismo de potenciación demostrado experimentalmente, ofrece ventajas clínicas y económicas y representa una alternativa recomendable en el empleo práctico de estas drogas.

Combinación de relajantes musculares no despolarizantes: sinergismo de potenciación farmacológica / Combination of nondepolarizing muscle relaxants: synergism of potentiation

Introducción: El empleo de ciertas asociaciones de relajantes musculares no despolarizantes a dosis subterapéuticas, aprovechando su sinergismo de potenciación, es una alternativa útil para la práctica anestesiológica diaria. Objetivos: 1.- Desarrollar las bases farmacológicas del fenómeno sinérgico, 2.- comentar los modelos experimentales y el análisis estadístico que lo avalan, 3.- enumerar las ventajas clínicas de su empleo y 4.- revisar y poner al día la bibliografía sobre el tema. Discusión: Desde las primeras observaciones en 1969, con la mezcla d-tubocurarina-gallamina, hasta la actualidad, con la asociación de los nuevos relajantes musculares no despolarizantes (atracurio-vecuronio, mivacurio-rocuronio, cisatracurio-rocuronio, etc.), este fenómeno de potenciación ha demostrado ofrecer ventajas tanto en el campo de la farmacología clínica como en el de la farmacoeconomía. Entre los mecanismos de potenciación propuestos, los más aceptados son los relacionados con la particular estructura del receptor nicotínico y con la combinación de mecanismos pre y postsinápticos en la unión neuromuscular. La comprobación experimental se acompaña de la determinación de las curvas dosis-respuesta, los gráficos de interacción y los análisis isobolográfico y algebraico. Las ventajas clínicas del fenómeno estudiado son: 1.- empleo de dosis subterapéuticas, con mayor margen de seguridad para los efectos cardiovasculares, 2.- menor tiempo de latencia, 3.- duración clínica y tiempos de recobro generalmente más breves que con los componentes aislados, 4.- adecuado grado de bloqueo neuromuscular, 5.- predictibilidad para los tiempos de administración y recuperación, 6.- fácil reversión con neotigmina y 7.- menor costo. Conclusiones: El uso de combinaciones de relajantes musculares no despolarizantes, en virtud del sinergismo de potenciación demostrado experimentalmente, ofrece ventajas clínicas y económicas y representa una alternativa recomendable en el empleo práctico de estas drogas. (AU)

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists.

STUDY OBJECTIVE: To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists. DESIGN: Retrospective study. SETTING: University hospital departments of anesthesia and pharmacy. MEASUREMENTS AND MAIN RESULTS: We placed price labels on the vial caps of all muscle relaxants for a study period of 1 year. At the beginning of the investigation, we informed the anesthesiologists of the study, discussed the prices for different muscle relaxants, and encouraged utilizing less expensive muscle relaxants whenever possible without compromising patient care. The price labels on the vial caps served as visual reminders of the various costs of muscle relaxants during daily practice. We compared the total amount spent on each muscle relaxant during the period from October 1993 to September 1994 with the period from October 1994 to September 1995. The total number of surgical cases from October 1993 to September 1994 and from October 1994 to September 1995 was unchanged and equaled 20,389 and 20,358 cases, respectively. Expenditures for pancuronium increased 104.1%. Total expenditure decreased by 12.5%, with a net savings of $47,111. CONCLUSION: Expenditures for the less costly pancuronium increased while expenditures for vecuronium and atracurium decreased. Price labeling of muscle relaxants in conjunction with education reduces total pharmacy expenditure on muscle relaxants.