Comparison of rocuronium priming vs. standard rapid sequence intubation technique in emergency department patients requiring intubation.

OBJECTIVE: In our study, we aimed to compare the effect of standard rapid sequence intubation protocol and the application of rocuronium priming technique on the procedure time and hemodynamic profile. METHODS: Patients who applied to the emergency department and needed rapid sequence intubation were included in our study, which we conducted with a randomized controlled design. Randomization in the study was made according to the order of arrival of the cases. Rapid sequence intubation was performed in the standard group. In the priming group, 10% of the rocuronium dose was administered approximately 3 min before the induction agent. Intubation time, amount of drug used, vital signs, and end-tidal CO2 level before and after intubation used to confirm intubation were recorded. RESULTS: A total of 52 patients were included in the study, of which 26 patients were included in the standard group and 26 patients in the priming group. While intubation time was 121.2±21.9 s in the standard group, it was calculated as 68.4±11.6 s in the priming group (p<0.001). While the mean arterial pressure was 58.3±26.6 mmHg in the standard group after intubation, it was 80.6±21.1 mmHg in the priming group (p=0.002). CONCLUSION: It was observed that priming with rocuronium shortened the intubation time and preserved the hemodynamic profile better. CLINICAL TRIAL REGISTRATION NUMBER: NCT05343702.

Unraveling the molecular dynamics of sugammadex-rocuronium complexation: A blueprint for cyclodextrin drug design.

Sugammadex, marketed as Bridion™, is an approved cyclodextrin (CD) based drug for the reversal of neuromuscular blockade in adults undergoing surgery. Sugammadex forms an inclusion complex with the neuromuscular blocking agent (NMBA) rocuronium, allowing rapid reversal of muscle paralysis. In silico methods have been developed for studying CD inclusion complexes, aimed at accurately predicting their structural, energetic, dynamic, and kinetic properties, as well as binding constants. Here, a computational study aimed at characterizing the sugammadex-rocuronium system from the perspective of docking calculations, free molecular dynamics (MD) simulations, and biased metadynamics simulations with potential of mean force (PMF) calculations is presented. The aim is to provide detailed information about this system, as well as to use it as a model system for validation of the methods. This method predicts results in line with experimental evidence for both the optimal structure and the quantitative value for the binding constant. Interestingly, there is a less profound preference for the orientation than might be assumed based on electrostatic interactions, suggesting that both orientations may exist in solution. These results show that this technology can efficiently analyze CD inclusion complexes and could be used to facilitate the development and optimization of novel applications for CDs.

The efficacy and safety of using a combination of rocuronium and sugammadex for awake craniotomy anesthesia: A randomized clinical trial.

BACKGROUND: Awake craniotomy (AC) is a neurosurgical method for the resection of brain lesions located in eloquent areas to achieve maximal and safe resection. A patient's arousal quality is essential for the success of the operation. This study compared the arousal time and quality after AC achieved by 2 different drug combinations: rocuronium with sugammadex and propofol with remifentanil. METHODS: This prospective, randomized, controlled trial included 42 adult patients undergoing AC with a laryngeal mask, who were randomly assigned to either a rocuronium-sugammadex group (RS; n = 21) or a propofol-remifentanil without muscle relaxant group (nRS; n = 21). The primary outcomes were the arousal time and arousal quality. The secondary outcomes included the number of laryngeal mask airway (LMA) adjustments and diaphragmatic excursion length. RESULTS: This study included 42 participants. The median (IQR) arousal time was 13.5 minutes (7-20) in the RS group and 21 minutes (16.5-26.5) in the nRS group (P = .005). There was no significant difference in arousal quality between the 2 groups (P = .229). LMA adjustments were significantly less frequent in the nRS group than in the RS group [0.25 times (±0.62) vs 1.26 times (±1.17), P = .001]. Adverse events, such as spontaneous movements and brain swelling, were more frequent in the nRS group than in the RS group. CONCLUSIONS: Using a combination of rocuronium and sugammadex with propofol and remifentanil may shorten the awakening time, reduce the duration of laryngeal mask adjustment, and do not affect the arousal quality and postoperative outcomes for patients undergoing awake craniotomy, compared to propofol and remifentanil alone.

Pillar[6]MaxQ functions as an in vivo sequestrant for rocuronium and vecuronium.

The binding affinity of pillar[6]MaxQ toward a panel of neuromuscular blockers and neurotransmitters was measured in phosphate buffered saline by isothermal titration calorimetry and 1H NMR spectroscopy. In vivo efficacy studies showed that P6MQ sequesters rocuronium and vecuronium and reverses their influence on the recovery of the train-of-four (TOF) ratio.

Effects of a single dose of rocuronium in patients with different body fat percentages: A randomised controlled trial.

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.

The Relationship between Pre-Anesthetic Analgesia and Nociception (ANI) and Propofol Injection Pain among Patients Receiving Remifentanil: A Prospective, Randomized, Controlled Study.

Background and Objectives: The analgesia/nociception index (ANI) potentially monitors nociceptive status during anesthesia, but its link to preoperative pain sensitivity is unclear. We investigated the relationship between pre-anesthetic ANI scores and propofol injection pain (PIP) in patients receiving remifentanil. Materials and Methods: This study included 124 male patients aged 19-60 undergoing general anesthesia (ASA class I or II). Patients were randomized to group R (n = 62, remifentanil 4 ng/mL) or group C (n = 62, saline). The primary outcome was the association between PIP and ANI. Secondary outcomes included the incidence and severity of PIP or rocuronium-induced withdrawal movement (RIWM) and their association with ANI. Results: PIP and RIWM incidence and severity were lower in group R than in group C. A weak negative correlation between PIP and ANI at pre-induction (rpb = -0.21, p = 0.02, rpb = -0.37, p < 0.01) and a moderate negative correlation during propofol injection (rpb = -0.48, p = 0.02) were observed. A significant negative correlation was found between RIWM and ANI during rocuronium injection (τb = -0.61, p < 0.01). AUC, cut-off value, specificity, and sensitivity in ANI at pre-induction for predicting PIP were 0.67 (p = 0.02), 59, 76%, and 55%, respectively. AUC, cut-off value, specificity, and sensitivity in ANI during propofol injection for PIP were 0.77 (p < 0.01), 65, 81%, and 67%, respectively. Conclusions: ANI scores demonstrated significant differences between groups, suggesting potential predictive value for PIP despite the low pre-induction AUC value. This study highlights the potential of using ANI scores to predict and manage PIP in patients receiving remifentanil.

Extravascular injection of neuromuscular blocking drugs: A systematic review of current evidence and management.

Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.

Cardiorespiratory consequences of attenuated fentanyl and augmented rocuronium dosing during protocolised prehospital emergency anaesthesia at a regional air ambulance service: a retrospective study.

BACKGROUND: Pre-Hospital Emergency Anaesthesia (PHEA) has undergone significant developments since its inception. However, optimal drug dosing remains a challenge for both medical and trauma patients. Many prehospital teams have adopted a drug regimen of 3 mcg/kg fentanyl, 2 mg/kg ketamine and 1 mg/kg rocuronium ('3:2:1'). At Essex and Herts Air Ambulance Trust (EHAAT) a new standard dosing regimen was introduced in August 2021: 1 mcg/kg fentanyl, 2 mg/kg ketamine and 2 mg/kg rocuronium (up to a maximum dose of 150 mg) ('1:2:2'). The aim of this study was to evaluate the cardiorespiratory consequences of a new attenuated fentanyl and augmented rocuronium dosing regimen. METHODS: A retrospective study was conducted at EHAAT as a service evaluation. Anonymized records were reviewed from an electronic database to compare the original ('3:2:1') drug dosing regimen (December 2019-July 2021) and the new ('1:2:2') dosing regimen (September 2021-May 2023). The primary outcome was the incidence of absolute hypotension within ten minutes of induction. Secondary outcomes included immediate hypertension, immediate hypoxia and first pass success (FPS) rates. RESULTS: Following exclusions (n = 121), 720 PHEA cases were analysed (360 new vs. 360 original, no statistically significant difference in demographics). There was no difference in the rate of absolute hypotension (24.4% '1:2:2' v 23.8% '3:2:1', p = 0.93). In trauma patients, there was an increased first pass success (FPS) rate with the new regimen (95.1% v 86.5%, p = 0.01) and a reduced incidence of immediate hypoxia (7.9% v 14.8%, p = 0.05). There was no increase in immediate hypertensive episodes (22.7% vs. 24.2%, p = 0.73). No safety concerns were identified. CONCLUSION: An attenuated fentanyl and augmented rocuronium dosing regimen showed no difference in absolute hypotensive episodes in a mixed cohort of medical and trauma patients. In trauma patients, the new regimen was associated with an increased FPS rate and reduced episodes of immediate hypoxia. Further research is required to understand the impact of such drug dosing in the most critically ill and injured subpopulation.

Efficacy and safety of adamgammadex for reversing rocuronium-induced deep neuromuscular blockade: A multicenter, randomized, phase IIb study.

The rapid reversal of deep neuromuscular blockade (NMB) is important but remains challenging. This study aimed to evaluate the efficacy and safety of adamgammadex versus sugammadex in reversing deep rocuronium-induced NMB. This multicenter, randomized, phase IIb study included 80 patients aged 18-64 years, American Society of Anesthesiologists (ASA) grade 1-2, undergoing elective surgery under general anesthesia with rocuronium. Patients were randomized to the adamgammadex 7, 8, and 9 mg/kg group or the sugammadex 4 mg/kg group. The primary efficacy variable was the time to recovery of train-of-four ratio (TOFr) to 0.9. The secondary efficacy variables were the time to recovery of TOFr to 0.7, antagonistic success rate of the recovery of TOFr to 0.9 within 5 min, and incidence rate of recurarization within 30 min after drug administration. The explorative efficacy variable was the time to recovery of the corrected TOFr to 0.9 (actual/baseline TOF ratio). Adamgammadex 7, 8, and 9 mg/kg and sugammadex 4 mg/kg groups did not significantly differ in all efficacy variables. Importantly, adamgammadex 9 mg/kg permitted reversal within a geometric mean of 2.9 min. According to the safety profile, adamgammadex achieved good tolerance and low incidence of drug-related adverse events compared with the 4 mg/kg sugammadex. Adamgammadex 7, 8, and 9 mg/kg facilitated rapid reversal of deep rocuronium-induced NMB and had good tolerance and low incidence of drug-related adverse events. Therefore, adamgammadex is a potential and promising alternative to sugammadex.

Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment: A Randomized, Double-Blinded Study.

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.

Are changes in antibiotic prophylaxis recommendations responsible for an increased risk of cefazolin allergy?

BACKGROUND: The first line of prevention of surgical site infection relies on the timely administration of antibiotic prophylaxis. First- and second-generation cephalosporins are the most recommended antibiotics in elective surgery. The incidence of cefazolin allergy has increased worldwide over the years. The sensitization mechanism of cefazolin is currently unknown, and data supporting cross-reactivity between penicillins and cephalosporins are lacking. Sensitization could occur through previous exposure either to cefazolin or to structurally related chemical agents. The objective of this study was to evaluate sensitization agents towards cefazolin. METHODS: The OpenBabel chemoinformatics toolbox was used to search for similarities between cefazolin and other molecules in an extensive drug database. Using the pholcodine-rocuronium similarity score as a threshold, we selected drugs with the most similar structure to that of cefazolin. Exposure to those drugs and cefazolin was assessed in a cohort of patients with skin test-proven cefazolin allergy at a specialized allergy centre via a self-administered anonymous questionnaire. RESULTS: Using the pholcodine-rocuronium similarity score as a threshold (score≥0.7), 42 molecules were found to be similar to cefazolin (all cephalosporins). Only 8 were marketed in France. None of the 14 cefazolin-allergic patients who answered the questionnaire (65% female, median age 56 years) reported exposure to any identified antibiotics. In contrast, 11 (78%) had at least one previous surgery requiring cefazolin before the index case. CONCLUSION: Direct previous cefazolin exposure was identified in 78% of cefazolin-allergic patients. Cefazolin started to take a central place in antibiotic prophylaxis after 2010, when cefamandole usage decreased drastically. Changes in antibiotic prophylaxis over the past 14 years in France could have been the turning point for the increased incidence of cefazolin allergy.

Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Effects of propofol versus sevoflurane on surgical field visibility during arthroscopic rotator cuff repair: a randomized trial.

BACKGROUND: During arthroscopic rotator cuff repair (ARCR), clear surgical field visibility (SFV) is the basis of successful surgery, but the choice of anesthesia maintenance drugs may have different effects on SFV. In this study, we aimed to compare the effects of propofol- and sevoflurane-based general anesthesia on SFV in patients undergoing ARCR. METHODS: Patients (n = 130) undergoing elective ARCR in the lateral decubitus position were randomized into either the propofol group or sevoflurane group (65 per group). The duration of surgery and increased pressure irrigation (IPI), Boezaart score, rocuronium consumption and usage of remifentanil were recorded. The time of both spontaneous respiration recovery and extubation and the incidences of postoperative nausea and vomiting and agitation were also recorded. RESULTS: The Boezaart score, duration of IPI and ratio of the duration of IPI to the duration of surgery (IPI/S ratio) were similar between the groups (P > 0.05). Rocuronium consumption, number of patients requiring remifentanil infusion and total remifentanil consumption were significantly lower in the sevoflurane group (P < 0.05). The spontaneous respiration recovery time was significantly longer in the propofol group (P < 0.05), but there were no differences in the extubation time between the groups(P > 0.05). CONCLUSIONS: Compared with propofol, sevoflurane provides equally clear SFV while improving the convenience of anesthesia maintenance in ARCR patients with interscalene plexus (ISB) combined with general anesthesia. TRIAL REGISTRATION: This single-center, prospective, RCT was retrospective registered at Chinese Clinical Trial Registry with the registration number ChiCTR2300072110 (02/06/2023).

Rocuronium Dosing by Ideal vs Total Body Weight in Obesity: A Prospective, Observational Non-inferiority Study.

Background: Providing adequate paralysis and appropriate sedation is challenging in patients with obesity during rapid sequence intubation (RSI). Pharmacokinetic parameters play an important role in dosing of rocuronium due to low lipophilicity. Rocuronium may be dosed based on ideal body weight (IBW). Current guidelines do not offer recommendations for dosing in the setting of obesity. Dosing depends on clinician preference based on total body weight (TBW) or IBW. Objective: In this study we performed non-inferiority analysis to compare the intubation conditions, duration of paralysis, and incidence of new-onset tachycardia or hypertension after intubation in obese patients requiring RSI in the emergency department (ED). Methods: This was a single-center, prospective, observational study. Eligible for enrollment were adult patients with a TBW ≥30% IBW or body mass index ≥30 kilograms per meters squared who presented to the ED requiring RSI with the use of rocuronium. Rocuronium was dosed according to intubating physicians' preference. Physicians completed a survey assessing intubation conditions. Height and weight used for the calculation of the dose, the dose of rocuronium, time of administration, and time of muscle function recovery were recorded. Endpoints assessed included grading of view during laryngoscopy, first-past success, and duration of paralysis. Results: In total, 96 patients were included, 54 in TBW and 42 in IBW. The TBW cohort received a mean of 1 milligram per kilogram (mg/kg) compared to 0.71 mg/kg in the IBW group. Excellent intubation conditions were observed in 68.5% in the TBW group and 73.8% in the IBW group. The non-inferiority analysis for relative risk of excellent intubation was 1.12 (P = 0.12, [90% CI 0.80-1.50]). Conclusion: Non-inferiority analysis suggests that IBW dosing provides similar optimal intubation conditions when compared to TBW dosing, but the noninferiority comparison did not reach statistical significance. This study was unable to show statistical non-inferiority for IBW dosing.

Quantitative evaluation of the biomechanical and viscoelastic properties of the dog patellar tendon in response to neuromuscular blockade at different stifle angles.

The patellar tendon (PT) is crucial for maintaining stability and facilitating movement in the stifle joint. Elastography has been recognized as a prominent method for evaluating PT properties in humans and dogs. The utilization of oscillation methods in canine studies remains limited despite their extensive documentation in human studies. Our study represents the first effort to quantitatively assess and compare the effects of muscle relaxant on the biomechanical and viscoelastic characteristics of the PT at varying stifle angles in living dogs. Five healthy female beagles were used in this study. Biomechanical (tone, stiffness, and decrement) and viscoelastic (relaxation time and creep) properties of the PT were measured using MyotonPRO (Myoton Ltd, Estonia) prior to and following administration of rocuronium (0.5 mg/kg/body weight) at normal, extended, and flexed positions. Rocuronium was selected for its safety, controllability, and widespread clinical use in veterinary anesthesia. Two-way analysis of variance showed that tone, stiffness, and decrement were significantly higher (P < 0.001) in the control group than in the muscle relaxation group. At the same time, relaxation time and creep were significantly lower (P < 0.001) in the control group than in the muscle relaxation group. The findings indicate that stifle angle position and muscle rexalant administration fundamentally alter the biomechanical loading conditions of the PT, leading to changes in its viscoelastic properties. Therefore, this novel quantitative data could benefit clinical settings that necessitate accurate and objective methods for risk identification and monitoring PT biomechanics in dogs.

Macrocycles and Acyclic Cucurbit[n]urils as Pseudo[2]catenane Partners for Long-Acting Neuromuscular Blocks and Rapid Reversal In Vivo.

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.

Comparison of the passive mast cell activation test with the basophil activation test for diagnosis of perioperative rocuronium hypersensitivity.

BACKGROUND: Rocuronium is a major cause of perioperative hypersensitivity (POH). Skin tests (STs) and quantification of specific immunoglobulin E antibodies (sIgEs) can yield incongruent results. In such difficult cases, the basophil activation test (BAT) can be helpful. Here, we evaluated the passive mast cell activation test (pMAT) as a substitute of BAT as part of the diagnostic tests for rocuronium allergy. METHODS: Sera from patients with a suspected POH reaction potentially related to rocuronium were included. All patients had a complete diagnostic investigation, including STs, quantification of sIgEs to morphine and rocuronium, and BAT. For execution of pMAT, human mast cells were generated from healthy donor peripheral blood CD34+ progenitor cells and sensitised overnight with patient sera. RESULTS: In total, 90 sera were studied: 41 from ST+sIgE+ patients, 13 from ST-sIgE- patients, 20 from ST+sIgE- patients, and 16 from ST-sIgE+ patients. According to BAT results, patients were further allocated into subgroups. Of the 38 BAT+ patients, 25 (66%) showed a positive pMAT as well. Of the 44 BAT- patients, 43 (98%) also showed a negative pMAT. Mast cells that were not passively sensitised did not respond to rocuronium. CONCLUSIONS: We show that the pMAT, in many cases, can substitute for BAT in the diagnosis of rocuronium hypersensitivity and advance diagnosis in difficult cases with uncertain ST or sIgE results when BAT is not locally available.