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Clinical Features and Management of Snakebite Envenoming in French Guiana

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Clinical Features and Management of Snakebite Envenoming in French Guiana toxins Article Clinical Features and Management of Snakebite Envenoming in French Guiana Dabor Resiere 1,2 , Stéphanie Houcke 1, Jean Marc Pujo 3, Claire Mayence 1, Cyrille Mathien 1, Flaubert NkontCho 4, Nicaise Blaise 4, Magalie Pierre Demar 5, Didier Hommel 1 and Hatem Kallel 1,* 1 Intensive Care Unit, Cayenne General Hospital, 97300 Cayenne, French Guiana, France; [email protected] (D.R.); [email protected] (S.H.); [email protected] (C.M.); [email protected] (C.M.); [email protected] (D.H.) 2 Intensive Care Unit, Martinique University Hospital, 97261 Martinique, France 3 Emergency Department, Cayenne General Hospital, 97300 Cayenne, French Guiana, France; [email protected] 4 Pharmacy Department, Cayenne General Hospital, 97300 Cayenne, French Guiana, France; fl[email protected] (F.N.); [email protected] (N.B.) 5 Laboratory department, Cayenne General Hospital, 97300 Cayenne, French Guiana, France; [email protected] * Correspondence: [email protected] Received: 23 September 2020; Accepted: 14 October 2020; Published: 19 October 2020 Abstract: The management of snakebite (SB) envenoming in French Guiana (FG) is based on symptomatic measures and antivenom (AV) administration (Antivipmyn Tri®; Instituto Bioclon—Mexico). Our study aimed to assess clinical manifestations, the efficacy, and safety of Antivipmyn Tri® in the management of SB. Our study is a prospective observational work. It was conducted in the Intensive Care Unit (ICU) of Cayenne General Hospital between 1 January 2016 and 31 December 2019. We included all patients hospitalized for SB envenoming. Our study contained three groups (without AV, three vials, and six vials Antivipmyn Tri®). During the study period, 133 patients were included. The main clinical symptoms were edema (98.5%), pain (97.7%), systemic hemorrhage (18%), blister (14.3%), and local hemorrhage (14.3%). AV was prescribed for 83 patients (62.3%), and 17 of them (20%) developed early adverse reactions. Biological parameters at admission showed defibrinogenation in 124 cases (93.2%), International Normalized Ratio (INR) > 2 in 104 cases (78.2%), and partial thromboplastin time (PTT) > 1.5 in 74 cases (55.6%). The time from SB to AV was 9:00 (5:22–20:40). The median time from SB to achieve a normal dosage of fibrinogen was 47:00 vs. 25:30, that of Factor II was 24:55 vs. 15:10, that of Factor V was 31:42 vs. 19:42, and that of Factor VIII was 21:30 vs. 10:20 in patients without and with AV, respectively, (p < 0.001 for all factors). Patients receiving Antivipmyn Tri® showed a reduction in the time to return to normal clotting tests, as compared to those who did not. We suggest assessing other antivenoms available in the region to compare their efficacy and safety with Antivipmyn Tri® in FG. Keywords: snakebite envenoming; clinical manifestations; French Guiana; Bothrops atrox; Antivipmyn Tri® Key Contribution: Antivipmyn Tri® can be an acceptable option in the correction of clotting tests in snake bitten patients in Franch Guiana Toxins 2020, 12, 662; doi:10.3390/toxins12100662 www.mdpi.com/journal/toxins Toxins 2020, 12, 662 2 of 13 1. Introduction Snakebite (SB) envenoming is a frequent event in French Guiana which can cause severe disabilities, or even death [1,2]. Its management requires symptomatic measures and antivenom administration [3]. More than 99 snake species have been identified in French Guiana, of which 12 are venomous, and five of these (Bothrops atrox, Bothrops brazili, Bothrops bilineatus, Lachesis muta and Micruruss sp) are responsible for most cases of envenomation [4]. Antivenom (Antivipmyn Tri®; Instituto Bioclon—Mexico) was introduced in Saint Laurent du Maroni Hospital (Western French Guiana) in 2014 in the frame of a collaboration with the Western France Poison Control Center, to establish a protocol to use an available and efficient antivenom in French Guiana [5]. Antivipmyn Tri® was the sole antivenom against the genus Bothrops authorized for use by the French authorities and available in the national antivenom bank. In January 2017, a 39-year-old man died from severe hemorrhagic complication after being bitten by a snake, presumably Bothrops atrox, in Cayenne (the capital city of French Guiana). At that time there was no available antivenom in Cayenne and snake-bitten patients were managed symptomatically [2]. In 2017, the French Authorities of Health recommended Antivipmyn Tri® for general use at the three main hospitals of French Guiana. Moreover, in September 2017, an international symposium was held at Cayenne under the aegis of the French Regional Health Agency and the Pan American Health Organization [5]. The conclusions of this symposium illustrated the urgent need to ensure the accessibility of effective and safe polyvalent viperid antivenom in French Guiana. In addition, experts stressed the need for post-marketing surveillance to confirm the efficacy of the antivenom used, to define the optimal dosage, and to check for adverse reactions. Common end-points for efficacy were defined as mortality, time taken to restore blood coagulability, halting of hemorrhage, and the importance and reversibility of other clinical manifestations [5]. Our study aimed to assess the clinical manifestations, efficacy, and safety of the antivenom Antivipmyn Tri® in the treatment of snakebites in French Guiana. 2. Results During the study period, 133 patients were admitted to the Intensive Care Unit (ICU) with a diagnosis of snakebite envenoming (on average 44 cases per year). Antivenom was used with 83 patients (62.4%). It was stopped after administration of one or two vials in seven cases (5.2%) because of early adverse reaction. In 76 patients (57.1%), the dose administered was 3 to 6 vials. Of these 76 patients, 14 (18.4%) received 3 vials, 59 (77.6%) received 6 vials, and 3 (3.9%) received 4 to 5 vials. In these three patients, the antivenom administration was stopped because of early adverse reaction. Figure1 summarizes the distribution of patients according to the antivenom dosage. Figure 1. Flowchart showing the distribution of patients according to antivenom dosage. (AV: Antivenom). The median age of patients was 42 years (28–52) and 70% were male. The median time from snakebite to admission to the ICU was 19:00 (5:03–22:03) and the median time between snakebite Toxins 2020, 12, 662 3 of 13 and antivenom administration was 9:00 (5:22–20:40). Snake identification was performed in 51% of cases. It was Bothrops atrox in 58 patients (43.6%). The main clinical symptoms were edema (98.5%), pain (97.7%), systemic hemorrhage (18%), blister (14.3%), and local hemorrhage (14.3%). The elapsed time from snakebite to the development of systemic hemorrhage was 4.5 h (inter-quartile range (IQR): 0–24). Infection was recorded in 32% of cases. It includes abscess (65%), necrotizing fasciitis (18.6%), and cellulitis (27.9%). Time from snakebite to infection was 6 days (IQR: 3–8). Table1 summarizes the epidemiological and clinical parameters of our patients. Table 1. Epidemiological and clinical parameters of our patients. All Patients Without Antivenom With Antivenom p Parameter Nb Result Nb Result Nb Result Age, years 133 42 (28–52) 50 47 (28–53) 76 40 (29–52) 0.595 Male gender 133 93 (69.9%) 50 37 (74%) 76 52 (68.4%) 0.501 BMI, Kg/m2 117 24 (21–27) 48 24 (22–27) 62 24 (21–27) 0.866 SAPS 133 13 (6–18) 50 13 (8–19) 76 13 (6–18) 0.127 History 133 40 (30.1%) 50 14 (28%) 76 24 (31.6%) 0.668 Hypertension 133 11 (8.3%) 50 2 (4%) 76 8 (10.5%) 0.185 Alcohol abuse 133 6 (4.5%) 50 4 (8%) 76 2 (2.6%) 0.166 Duration Time from SB to Hospitalization 133 7:30 (2:00–11:00) 50 11:55 (5:00–27:30) 76 5:12 (1:08–18:05) 0.000 Time from Hospitalization to ICU 128 1:39 (0:00–6:22) 50 3:15 (0:00–6:04) 71 1:30 (0:00–3:55) 0.020 Time from SB to ICU 128 19:00 (5:03–22:03) 50 18:35 (9:33–27:37) 71 9:00 (4:45–18:10) 0.000 Snake Bite Grade I envenomation 133 51 (38.3%) 50 14 (28%) 76 32 (42.1%) 0.108a Grade II envenomation 133 47 (35.3%) 50 18 (36%) 76 28 (36.8%) 0.381b Grade III envenomation 133 35 (26.2%) 50 18 (36%) 76 16 (21.1%) 0.064c Clinical features Snake identification 133 68 (51.1%) 50 24 (48%) 76 39 (51.3%) 0.716 Oedema 133 131 (98.5%) 50 49 (98%) 76 75 (98.7%) 0.764 Nb of involved segments 133 2 (1–3) 50 2 (2–3) 76 2 (1–2) 0.091 Local hemorrhage 133 19 (14.3%) 50 5 (10%) 76 14 (18.4%) 0.196 Necrosis 133 14 (10.5%) 50 5 (10%) 76 9 (11.8%) 0.748 Blister 133 19 (14.3%) 50 15 (30%) 76 4 (5.3%) 0.000 Pain 133 130 (97.7%) 50 47 (94%) 76 76 (100%) 0.031 Mean arterial pressure, mmHg 133 95 (88–102) 50 93 (86–103) 76 95 (89–102) 0.578 Cardiac rythm, beat/min 133 78 (67–91) 50 84 (72–94) 76 76 (66–90) 0.213 Temperature (◦C) 133 37 (37–37) 50 37 (37–38) 76 37 (37–37) 0.001 SpO2 (%) 133 99 (98–100) 50 99 (97–100) 76 100 (98–100) 0.274 Shock 133 2 (1.5%) 50 2 (4%) 76 0 (0%) 0.079 Renal failure 133 20 (15%) 50 10 (20%) 76 10 (13.2%) 0.304 Systemic hemorrhage 133 24 (18%) 50 12 (24%) 76 11 (14.5%) 0.176 BMI: Body Mass Index; SAPS: Simplified Acute Physiologic Score; SpO2: peripheral capillary oxygen saturation; a: Grade I compared to Grade II and III; b: Grade II compared to Grade I and III; c: Grade III compared to Grade I and II.
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