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.

Reducing Medication Waste While Improving Access to Sugammadex: A Quality Improvement Project in Medication Stewardship.

The relatively high cost of sugammadex compared to neostigmine limits its widespread use to reverse neuromuscular blockade, despite its faster onset and more complete clinical effect. While ensuring timely access to sugammadex is important in improving perioperative safety, it is also vital to control unnecessary spending. We describe a quality improvement initiative to reduce excess spending on sugammadex while improving access for anesthesia providers. Monthly spending on sugammadex decreased by 52% ($70,777 vs $33,821), while medication access increased via automated medication dispensers in each operating room. Clinical usage decreased by one-third, with presumed increased adherence to dosing guidelines.

Effect of a Cognitive Aid on Reducing Sugammadex Use and Associated Costs: A Time Series Analysis.

BACKGROUND: The authors observed increased pharmaceutical costs after the introduction of sugammadex in our institution. After a request to decrease sugammadex use, the authors implemented a cognitive aid to help choose between reversal agents. The purpose of this study was to determine if sugammadex use changed after cognitive aid implementation. The authors' hypothesis was that sugammadex use and associated costs would decrease. METHODS: A cognitive aid suggesting reversal agent doses based on train-of-four count was developed. It was included with each dispensed reversal agent set and in medication dispensing cabinet bins containing reversal agents. An interrupted time series analysis was performed using pharmaceutical invoices and anesthesia records. The primary outcome was the number of sugammadex administrations. Secondary outcomes included total pharmaceutical acquisition costs of neuromuscular blocking drugs and reversal agents, adverse respiratory events, emergence duration, and number of neuromuscular blocking drug administrations. RESULTS: Before cognitive aid implementation, the number of sugammadex administrations was increasing at a monthly rate of 20 per 1,000 general anesthetics (P < 0.001). Afterward, the monthly rate was 4 per 1,000 general anesthetics (P = 0.361). One month after cognitive aid implementation, the number of sugammadex administrations decreased by 281 per 1,000 general anesthetics (95% CI, 228 to 333, P < 0.001). In the final study month, there were 509 fewer sugammadex administrations than predicted per 1,000 general anesthetics (95% CI, 366 to 653; P < 0.0001), and total pharmaceutical acquisition costs per 1,000 general anesthetics were $11,947 less than predicted (95% CI, $4,043 to $19,851; P = 0.003). There was no significant change in adverse respiratory events, emergence duration, or administrations of rocuronium, vecuronium, or atracurium. In the final month, there were 75 more suxamethonium administrations than predicted per 1,000 general anesthetics (95% CI, 32 to 119; P = 0.0008). CONCLUSIONS: Cognitive aid implementation to choose between reversal agents was associated with a decrease in sugammadex use and acquisition costs.

Implementation of a new strategy to improve the peri-operative management of neuromuscular blockade and its effects on postoperative pulmonary complications.

Inappropriate dosing of neostigmine for antagonism of neuromuscular blockade has been associated with postoperative pulmonary complications. We evaluated the effects of a quality improvement initiative tailored to optimise the use of neostigmine in antagonising neuromuscular blockade on postoperative pulmonary complications, costs and duration of hospital stay. The quality improvement initiative consisted of: a reduction in available neostigmine aliquot sizes; a cognitive aid; an educational component; and a financial incentive for the intra-operative documentation of train-of-four measurement before administration of neostigmine. We conducted a pre-specified analysis of data obtained in our quality improvement study. Additional analyses were conducted in a propensity-matched cohort. An interrupted time series design was used to discriminate between the intervention and a counterfactual scenario. We analysed 12,025 consecutive surgical cases performed in 2015. Postoperative pulmonary complications occurred in 220 (7.5%) of 2937 cases pre-intervention and 568 (6.3%) of 9088 cases post-intervention. Adjusted regression analyses showed significantly a lower risk of postoperative pulmonary complications (OR 0.73 (95%CI 0.61-0.88); p = 0.001), lower costs (incidence rate ratio 0.95 (95%CI 0.93-0.97); p < 0.001) and shorter duration of hospital stay (incidence rate ratio 0.91 (95%CI 0.87-0.94); p < 0.001) after implementation of the quality improvement initiative. Analyses in a propensity-matched sample (n = 2936 per group) and interrupted time series analysis (n = 27,202 cases) confirmed the findings. Our data show that a local, multifaceted quality improvement initiative can enhance the quality of intra-operative neuromuscular blocking agent utilisation, thereby reducing the incidence of postoperative pulmonary complications.

Operating room discharge after deep neuromuscular block reversed with sugammadex compared with shallow block reversed with neostigmine: a randomized controlled trial.

OBJECTIVE: To determine if reversing a deep or moderate block with sugammadex, compared with a shallow block reversed with neostigmine, reduces the time to operating room discharge after surgery and the time spent in the postanesthesia care unit. DESIGN: A randomized controlled trial. SETTING: Monocentric study performed from February 2011 until May 2012. PATIENTS: One hundred consenting women with American Society of Anesthesiologists grade I or II were randomized into 2 groups. INTERVENTION: Laparoscopic hysterectomy was performed under desflurane general anesthesia. For the neostigmine (N) group, 0.45 mg · kg-1 rocuronium was followed by spontaneous recovery. A 5-mg rescue bolus was administered only if surgical evaluation was unacceptable. At the end of surgery, 50 µg · kg-1 neostigmine with glycopyrrolate was administered. For the sugammadex (S) group, a higher intubating rocuronium dose (0.6 mg · kg-1) was followed by 5-mg boluses each time the train-of-four count exceeded 2. Sugammadex (2-4 mg · kg-1) was administered to reverse the block. All patients were extubated after obtaining a train-of-four ratio of 0.9. MEASUREMENTS: The duration between the end of surgery and operating room discharge and the time spent in the postanesthesia care unit. MAIN RESULTS: The time till operating room discharge was shorter and more predictable in group S (9.15±4.28 minutes vs 13.87±11.43 minutes in group N; P=.005). The maximal duration in group S was 22 minutes, compared with 72 minutes in group N. The time spent in the postanesthesia care unit was not significantly different (group S: 47.75±31.77 minutes and group N: 53.43±40.57 minutes; P=.543). CONCLUSION: Maintaining a deep neuromuscular block during laparoscopic hysterectomy reversed at the end of the procedure with sugammadex enabled a faster and more predictable time till operating room discharge than did the classical combination of a shallower block reversed with neostigmine.

Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia?

PURPOSE OF REVIEW: Sugammadex is a selective relaxant-binding agent that is designed to encapsulate rocuronium and chemically similar steroidal muscle relaxants such as vecuronium. This review summarizes recent information on the use of sugammadex in clinical practice. RECENT FINDINGS: The main advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and its unique ability to reverse rapidly and efficiently, for the first time, deep levels of neuromuscular blockade. However, there is paucity of evidence-based studies on the benefit of deep neuromuscular block, and then routine administration of sugammadex to reverse any level of block, for example, during laparoscopic surgery. It appears that reduction of costs depends mainly on organizational factors. Finally it must be remembered that sugammadex only works with steroidal nondepolarizing muscle relaxants; therefore neostigmine should not be withdrawn because it is the only reversal agent effective against atracurium or cisatracurium. SUMMARY: Sugammadex offers a significantly faster and more predictable recovery profile than neostigmine. It is now possible to reverse rapidly and efficiently any level of neuromuscular blockade and to avoid the risk of adverse events because of residual paralysis such as critical respiratory events during recovery from anesthesia.

Unrestricted access to sugammadex: impact on neuromuscular blocking agent choice, reversal practice and associated healthcare costs.

Sugammadex is known to rapidly and completely reverse the effects of amino-steroidal neuromuscular blocking agents. However, the high costs of sugammadex have so far prevented its introduction as the standard reversal agent in most healthcare systems. At the Royal Perth Hospital, sugammadex was recently introduced as an unrestricted alternative to neostigmine for the reversal of amino-steroidal neuromuscular blocking agents. The aim of this retrospective observational audit was to investigate the impact of this change on clinical practice and associated healthcare costs. Data from all patients intubated during a one-month period in April to May 2010 and for a similar period in 2011 were retrospectively collected and the use of neuromuscular blocking agents and reversal agents were identified and the associated costs were calculated. More steroidal neuromuscular blocking agents and sugammadex (+743%), but less glycopyrrolate and neostigmine (-48%) were used in 2011. Using the manufacturer's list price, muscle relaxation and reversal costs increased from about A$42 per case to about A$127 per case. Between the investigated time periods no differences were found for anaesthesia time, operating time or time spent in the post anaesthesia care unit. However, there was a statistically significant decrease in the time between surgery and discharge (median 2.0 vs 2.2 days). While the design of the audit was such that no inferences can be made about the cause of this change, this is an interesting observation worthy of further investigation.

Sugammadex for reversal of neuromuscular block after rapid sequence intubation: a systematic review and economic assessment.

Sugammadex 16 mg kg⁻¹ can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a 'can't intubate, can't ventilate' (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.

Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation.

The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the 'value of time saved' which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg⁻¹ (4 mg kg⁻¹) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources.

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? METHODS: The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. RESULTS: Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5%-95% percentiles $42,259-$83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. CONCLUSION: ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS.

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.