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• W4205280797 abstract "Editor—Snake envenomation is a common medical emergency encountered mainly in tropical countries. About 2.5 million individuals are bitten by snakes annually. Of these, 1.8 million develop clinical illness, and 81 000 to 138 000 die from complications.1Williams D.J. Faiz M.A. Abela-Ridder B. et al.Strategy for a globally coordinated response to a priority neglected tropical disease: snakebite envenoming.PLoS Negl Trop Dis. 2019; 13e0007059Crossref Scopus (187) Google Scholar The elapid snakebite predominantly causes neurotoxicity, which manifests as ocular and bulbar paralysis followed by respiratory muscle paralysis and respiratory failure.2Agarwal R. Singh N. Gupta D. Is the patient brain-dead?.Emerg Med J. 2006; 23: e5Crossref PubMed Scopus (19) Google Scholar In neuroparalytic snake envenomation, conventional modes of mechanical ventilation (volume or pressure cycled) are used during the initial few hours for ventilating these patients, because of profound respiratory muscle weakness. Subsequently, a majority of the time on mechanical ventilation is spent on the process of weaning. Even after the resolution of respiratory failure, many patients are ventilated with the assist control mode, which delays the process of discontinuation from assisted ventilation. Moreover, weaning is accomplished using the pressure support mode to overcome the work of breathing imposed by artificial airways.3Aggarwal A.N. Agarwal R. Gupta D. Automatic tube compensation as an adjunct for weaning in patients with severe neuroparalytic snake envenomation requiring mechanical ventilation: a pilot randomized study.Respir Care. 2009; 54: 1697-1702PubMed Google Scholar However, during pressure support ventilation, only a fixed level of pressure support is provided with each breath despite changing lung mechanics. Adaptive support ventilation, a closed-loop ventilation mode, automatically selects ventilatory parameters to minimise the total work of inspiration.4Sehgal I.S. Kalpakam H. Dhooria S. Aggarwal A.N. Prasad K.T. Agarwal R. A randomized controlled trial of noninvasive ventilation with pressure support ventilation and adaptive support ventilation in acute exacerbation of COPD: a feasibility study.COPD. 2019; 16: 168-173Crossref PubMed Scopus (11) Google Scholar Notably, during adaptive support ventilation, the ventilator automatically switches between the controlled and the spontaneous modes depending on spontaneous respiratory efforts. By reducing the time to onset of weaning and optimising work of breathing, adaptive support ventilation is likely to reduce the duration of mechanical ventilation by allowing early resumption of spontaneous breathing. In a previous study, adaptive support ventilation reduced weaning duration and total duration of mechanical ventilation in patients with acute respiratory failure compared with volume-cycled ventilation.5Kirakli C. Naz I. Ediboglu O. Tatar D. Budak A. Tellioglu E. A randomized controlled trial comparing the ventilation duration between adaptive support ventilation and pressure assist/control ventilation in medical patients in the ICU.Chest. 2015; 147: 1503-1509Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar We hypothesised that adaptive support ventilation would reduce the duration of mechanical ventilation in patients with neuroparalytic snake envenomation. Herein, we compare the duration of mechanical ventilation in patients with neuroparalytic snake envenomation using either the adaptive support ventilation or the volume-cycled ventilation mode. We conducted an investigator-initiated, single-centre, parallel-group, RCT between September 2016 and January 2020 in the respiratory ICU of the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. The institute ethics committee approved the study protocol (NK/2194/Study/1241[168]). We obtained informed consent from next of kin. The trial was registered at www.clinicaltrials.gov (NCT02877498). We randomised (1:1) consecutive victims of neuroparalytic snake envenomation with respiratory failure aged 12–90 yr and requiring invasive mechanical ventilation to either volume-cycled ventilation or adaptive support ventilation (Supplementary Fig. S1). We excluded subjects with any of the following: cardiorespiratory arrest requiring cardiopulmonary resuscitation, pregnancy, or failure to provide informed consent. We used a tidal volume of 6–8 ml kg−1 predicted body weight in subjects randomised to volume-cycled ventilation (Supplementary File S1). In the adaptive support ventilation arm, we ventilated all subjects with an initial setting of 100%-MinVol and PEEP of 5 cm H2O. Further increments were based on clinical parameters (Supplementary File S1). In both study arms, FiO2 was set to maintain SpO2 of 90–92% at minimum possible FiO2. Additionally, all subjects received polyvalent snake antivenom (Snake venom antiserum IP, Bharat Serums and Vaccines Ltd., Ambernath, India) in standard doses (100 ml at presentation followed by 100 ml after 6 h). We used sedation (midazolam) and analgesia (fentanyl) during mechanical ventilation but no neuromuscular blocking agents. In the volume-cycled ventilation arm, once the clinical condition stabilised and weaning criteria were met (Supplementary File S1), we placed the subject on pressure support mode. In the adaptive support ventilation arm, we performed weaning by gradually reducing the %MinVol (decrements of 10% per hour to a %MinVol of 60%). Once comfortable in the above settings, subjects underwent a 30-min spontaneous breathing trial on T-piece and monitored closely for signs of failure (Supplementary File S1). The primary outcome was time to liberation from mechanical ventilation (defined as time [in hours] between tracheal intubation to extubation for at least 24 h). The secondary outcomes were time to initiation of weaning, incidence of ventilator-associated pneumonia, post-extubation respiratory failure (defined as the need for either noninvasive ventilation or reintubation), hospital mortality, and ICU and hospital length of stay. Based on our previous experience, we assumed a mean (standard deviation [sd]) duration of mechanical ventilation of 48 (12) h in the conventional arm6Agarwal R. Aggarwal A.N. Gupta D. Behera D. Jindal S.K. Low dose of snake antivenom is as effective as high dose in patients with severe neurotoxic snake envenoming.Emerg Med J. 2005; 22: 397-399Crossref PubMed Scopus (43) Google Scholar and 36 h in the adaptive support ventilation arm. Using these assumptions, we required 21 subjects in each arm to achieve a power of 90% with alpha error of 0.05 and beta error of 0.1 (clincalc.com/stats/samplesize.aspx). Assuming a 10% dropout rate, we needed to enrol 47 subjects (n/1-dropout rate [42/0.9=46.7]). We expressed the results as numbers with percentages or mean (sd) or 95% confidence interval (CI) or median (inter-quartile range). We used the χ2 square test (or Fisher's exact test) and Mann–Whitney U-test (or Student's t-test) to analyse differences. Statistical significance was assumed at P<0.05. We randomised 48 subjects with neuroparalytic snake envenomation to either the volume-cycled ventilation arm (n=24) or the adaptive support ventilation arm (n=24) (Supplementary Fig. S1). We identified cellulitis or swelling at the site of snakebite in 11 subjects. The median (inter-quartile range) age of the study population (32 [66.7%] males) was 25 (19–35) yr (Supplementary Table S1). The mean time to presentation after snake bite was 5.1 (3.4) h and 5.6 (4.6) h in the volume-cycled ventilation and adaptive support ventilation arm, respectively. The mean dose of snake antivenom was similar between the two arms (196 [53] ml vs 228 [58] ml, volume-cycled ventilation vs adaptive support ventilation; P=0.09). Baseline clinical, respiratory, physiological, and ICU parameters were similar in the two groups (Supplementary Table S1). The median (inter-quartile range) %MinVol was 100 (100–150) in the adaptive support ventilation, arm. We found no difference in the time to extubation (Table 1) between study arms (estimate difference [95% CI], 6.6 [−51.9 to 65.1] h). Three subjects developed post-extubation respiratory failure that required noninvasive ventilation support (Table 1). The proportion of subjects who developed post-extubation respiratory failure was similar in the two groups. We found no difference in time to initiation of weaning or incidence of ventilator-associated pneumonia between groups. None of the subjects developed barotrauma. We recorded no deaths. There was no difference in the ICU or hospital length of stay.Table 1Outcome parameters. All values are expressed as mean (standard deviation) unless specified. ASV, adaptive support ventilation; LOS, length of stay; VCV, volume-cycled ventilation.ASV(n=24)VCV(n=24)Difference(95% confidence interval)P valuePrimary outcome Time to tracheal extubation, h90.4 (87.3)97 (112)6.6 (−51.9–65.1)0.95Secondary outcomes Time to initiation of weaning, h51.3 (50.9)53.3 (56.7)2 (−29.3–33.3)0.76 Post-extubation respiratory failure, n (%)2 (8.3)1 (4.2)2.1 (0.2–24.7)0.5 Mortality, n (%)00—— Ventilator-associated pneumonia, n (%)2 (8.3)1 (4.2)2.1 (0.2–24.7)0.5 Barotrauma, n (%)00—— ICU-LOS, days4.8 (3.8)5.5 (4.9)0.7 (−1.9–3.3)0.79 Hospital-LOS, days4.9 (3.8)5.7 (4.9)0.8 (−1.8–3.4)0.76 Open table in a new tab An estimated 40–50% of the time spent on a mechanical ventilator is during weaning.7Esteban A. Alía I. Ibañez J. Benito S. Tobin M.J. Modes of mechanical ventilation and weaning. A national survey of Spanish hospitals. The Spanish Lung Failure Collaborative Group.Chest. 1994; 106: 1188-1193Abstract Full Text Full Text PDF PubMed Scopus (346) Google Scholar By facilitating early resumption of spontaneous activity, adaptive support ventilation is likely to hasten recovery and weaning from mechanical ventilation.8Laubscher T.P. Frutiger A. Fanconi S. Jutzi H. Brunner J.X. Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.Int J Clin Monit Comput. 1994; 11: 19-30Crossref PubMed Scopus (49) Google Scholar However, ventilatory recovery was not hastened by adaptive support ventilation in our study, possibly because of the short duration of respiratory failure. The recovery of patients from neuroparalytic state in neuroparalytic snake envenomation also depends on the dose of toxin injected, the type of toxin (presynaptic [krait] vs postsynaptic [cobra]), and the time between snakebite and administration of snake antivenom.9Anil A. Singh S. Bhalla A. Sharma N. Agarwal R. Simpson I.D. Role of neostigmine and polyvalent antivenom in Indian common krait (Bungarus caeruleus) bite.J Infect Public Health. 2010; 3: 83-87Crossref PubMed Scopus (33) Google Scholar,10Alirol E. Sharma S.K. Ghimire A. et al.Dose of antivenom for the treatment of snakebite with neurotoxic envenoming: evidence from a randomised controlled trial in Nepal.PLoS Negl Trop Dis. 2017; 11e0005612Crossref PubMed Scopus (22) Google Scholar Our study is not without limitations. The small sample size and conduct at a single centre limits generalisability. The large CI around the primary outcome suggests imprecision of the results as a result of the small sample size. We also did not compare the number of ventilatory adjustments between the two arms. Finally, we could not document the type of snakebites because of the lack of availability of immunological tests for detecting the toxin. In summary, adaptive support ventilation did not reduce the duration of mechanical ventilation compared with volume-cycled ventilation in subjects with neuroparalytic snake envenomation and respiratory failure. However, adaptive support ventilation was safe as a single mode in subjects with acute respiratory failure as a result of neuroparalytic snake envenomation. The results of this study require confirmation in a larger multicentre trial. The authors declare that they have no conflicts of interest. The following is the Supplementary data to this article: Download .docx (.1 MB) Help with docx files Multimedia component 1" @default.
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• W4205280797 title "A randomised trial of adaptive support ventilation in patients with neuroparalytic snake envenomation" @default.
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