SUBMITTED 12 APR 23 1 REVISION REQ. 21 MAY 23; REVISION RECD. 31 MAY 23 2 ACCEPTED 12 JUL 23 3 ONLINE-FIRST: JULY 2023 4 DOI: https://doi.org/10.18295/squmj.7.2023.046 5 6 Efficacy of Ropivacaine for Sub-Arachnoid Block in Patients with Recent 7 History of Scorpion Sting 8 A case series 9 *Saurabh Trivedi, Hemendra Bhardwaj, Tapan K. Sahoo, 10 Seema Gupta 11 12 Department of Anaesthesia & Critical Care, Chirayu Medical College & Hospital, Bhopal, 13 India. 14 *Corresponding Author’s e-mail: drst23@gmail.com 15 16 Abstract 17 Failure of sub-arachnoid block (SAB), due to resistance to bupivacaine after a recent scorpion 18 sting can lead to multiple block attempts and subsequent conversion to general anaesthesia. 19 We report this case series of 10 patients with successful SAB with newly launched 0.75% 20 hyperbaric ropivacaine, in patients with recent scorpion sting. Thus, intrathecal hyperbaric 21 ropivacaine may be considered as the local anaesthetic agent of choice in patients with 22 scorpion sting to prevent failure of SAB. 23 Keywords: Bupivacaine; Ropivacaine; Scorpion sting; Spinal anaesthesia 24 25 Introduction 26 Spinal anesthesia or Sub-arachnoid block (SAB) is a commonly practised technique of 27 anaesthesia for most below-umbilical procedures.1 Clinical data has shown a correlation 28 between previous history of scorpion sting and resistance to SAB with bupivacaine, an 29 amino-amide local anaesthetic.2,3 30 31 Ropivacaine (2,6-dimethylphenyl, 1-propylpiperidine,2-carboxamide) is a piperidine-32 carboxamide- based amide, prepared as pure S-enantiomer.4 Multiple studies have shown that 33 ropivacaine is a safe and effective local anesthetic (LA) for regional anaesthesia techniques. 34 Hyperbaric preparation of ropivacaine (0.75%) for SAB have recently been launched in India, 35 and its efficacy and safety for intra-thecal administration has been documented.5 36 37 We report successful sub-arachnoid blockage with ropivacaine in patients with confirmed 38 history of recent scorpion sting. 39 40 Case series 41 This case series includes 10 patients of either gender, aged 18-70 years, with a history of 42 scorpion sting within 5 years, undergoing below umbilical surgeries under SAB, between 43 August 2022 and November 2022 at a tertiary care hospital of central India [Table 1]. 44 Patients with confirmed history of scorpion sting in pre-anaesthetic check-up , were further 45 evaluated for the number of stings, duration since last sting and severity of the sting [Grade 46 1- local pain & paraesthesia at the sting site, Grade 2- local pain and paraesthesia existing at 47 the sting site as well as proximal to the sting site, Grade 3- Grade 2 factors with added cranial 48 nerve (increased oral secretions, blurry vision, rapid tongue movement, nystagmus), or 49 skeletal neuromuscular dysfunction (flailing of the extremities and tetanus-like arching of the 50 back) with or without autonomic dysfunction, Grade 4- includes both cranial nerve and 51 skeletal muscle dysfunction, hyperthermia, rhabdomyolysis, pulmonary oedema, multiple 52 organ failures].6 53 54 A written-informed consent was obtained from all the patients for publication purposes. After 55 standard fasting of 8 hours, patients were shifted to operation theatre and standard monitors 56 applied and baseline vitals were noted. A single operator performed all the SAB, using 25 57 gauze, 90 mm Becton Dickinson (BD), Quinke needle, at L3-4 interspace in the sitting 58 position, with a standard dose of 3.2 mL, 0.75% hyperbaric ropivacaine. The patients were 59 positioned supine immediately after drug administration and assessment for autonomic, 60 sensory, and motor blockage was done by a blinded observer (trained anesthesiologist) 61 immediately after supine positioning. 62 63 Haemodynamic parameters were noted every minute for 5 minutes from the time of supine 64 positioning, and every 5 minutes afterwards for 20 minutes. 65 66 Sensory blockage was assessed using pin-prick method, using a two-point scoring system (0- 67 normal sensation, 1- loss of pain sensation but pressure sensation intact, 2 – loss of pain & 68 pressure sensation). A score of 1 and 2 at T10 level, were considered as onset and completion 69 of sensory block, respectively. 70 71 Bromage scale7 was used for motor blockage assessment. Bromage grade II and IV were 72 considered as onset and completion of motor block, respectively. The block was considered 73 adequate when a complete sensory and motor blockage was achieved at T-10 level, and 74 planned surgery was started. In case of inadequate blockage (a sensory score of 0 or 1 with 75 Bromage grade < IV) at 20 minutes after SAB, it was considered a block failure. On the 76 completion of surgery, patients were shifted to post-anaesthesia care units for monitoring. 77 The time for onset and completion of sensory and motor blockage, and block failure were 78 assessed for association with number, duration, and severity of sting. 79 80 Results 81 The mean time to onset of sensory and motor block was 78.8 and 94.2 seconds respectively, 82 and the mean time to completion of sensory and motor blockage was 117 and 146.7 seconds 83 respectively. All 10 patients achieved complete sensory and motor blockage within 20 84 minutes and none of the SAB failed. 85 86 Out of 10 patients, 5 patients had a history of single sting, 3 patients had 2-5 stings and 2 87 patients >5 stings. The mean time to onset and completion of sensory and motor blockage 88 was more in patients with history of multiple (>2) stings (Figure 1-A). Patients with sting 89 within one year had relatively faster onset of sensory and motor block as compared to 90 patients with sting between 1 to 5 years (Figure 1-B). Patients with clinical grade 2 and 3 91 sting had relatively delayed onset and completion of blockage (Figure 1-C). No episode of 92 post-spinal hypotension (fall in Mean Arterial Pressure (MAP) > 20% from baseline) was 93 observed in our patients, except patient 4 (Figure 2). 94 95 Discussion 96 Scorpion sting is a common occurrence in Indian sub-continent. Usually harmless, with 97 manifestations like severe pain, and burning sensation at the site of sting. Systemic 98 manifestations like myocardial infarction, acute pulmonary oedema, cardiogenic shock and 99 death are very rare.8 Thus, a large rural population coming for elective surgical procedures, 100 may give history of grades 1 or 2 sting.6 101 102 The scorpion venom is a weak acid (pH 6.5) and highly complex mixture of salts, 103 nucleotides, biogenic amines, enzymes, mucoproteins, and neurotoxins, acting on ion 104 channels specifically voltage gated sodium channels (VGSC). Out of various scorpion toxins, 105 alpha and beta toxins are known to bind to mammalian VGSC. The alpha toxin binds 106 extracellularly to S3-S4 loop in domain IV and extracellular part of segment S5-S6 of domain 107 I.9 The beta toxin binds to extracellular part of segment 4 of domain II.9 The binding site of 108 local anesthetics (LA) is segment 6 of domain IV of alpha subunit of VGSC.10 Panditrao et 109 al.2,3 had described the resistance to intrathecal bupivacaine in patients with a history of 110 scorpion sting, and postulated that scorpion toxin itself or the antibodies against the toxin are 111 responsible for the development of resistance to intrathecal bupivacaine. 112 113 Amrita et al.11 demonstrated adequate sensory and motor block after SAB with 0.75% 114 hyperbaric ropivacaine in 2 patients with a history of scorpion sting with documented 115 resistance to bupivacaine on subcutaneous LA testing. Similarly, the present case series 116 demonstrated successful sub-arachnoid block with 0.75% hyperbaric ropivacaine in 10 117 patients with a history of scorpion sting. Out of 10 patients, 5 patients had a history of single 118 sting, 3 patients had 2-5 stings and 2 patients >5 stings. The mean time to onset and 119 completion of sensory and motor blockage was more in patients with history of multiple (>2) 120 stings as compared to single sting. This may be due to the antibodies against scorpion venom 121 that had accumulated with multiple stings as postulated by Panditrao et al.2,3 122 Patients with sting history between 1-5 years had comparatively delayed onset and 123 completion of sensory and motor blockage as compared to patients with a sting within 1 year. 124 Patients with clinical grade 2 and 3 sting had relatively delayed onset and completion of 125 sensory and motor blockage. 126 127 Molecular modelling of local anesthetic binding with VGSC has demonstrated the differences 128 in the relative alignment of aromatic part of ropivacaine as compared to other LA on VGSC. 129 The aromatic part of ropivacaine aligns towards the outer side of VGSC whereas the aromatic 130 part of bupivacaine aligns towards the inner side of the channel.12,13 This differential 131 alignment of aromatic ring may contribute to the difference in resistance of the two LA 132 caused by scorpion sting. Further, action of ropivacaine on gamma aminobutyric acid A 133 (GABA-A) and N-methyl-D-aspartate (NMDA) receptors,14,15 facilitates its LA action, 134 thereby decreasing the chances of its resistance in patients with a scorpion sting. Thus, 135 differences in the three-dimensional structures of ropivacaine and bupivacaine may confer 136 differences in the activity of their enantiomers in the complex biological environment of the 137 receptors,4 and may be responsible for the success of intra-thecal ropivacaine in patients with 138 scorpion sting. 139 140 Conclusion 141 Intrathecal hyperbaric ropivacaine may be considered as the local anaesthetic agent of choice 142 in patients with scorpion sting to prevent failure of sub-arachnoid block. Further scientific 143 studies are needed to further validate these findings. 144 145 Authors’ Contribution 146 Concept and design of study was made by ST. ST, HB, TKS and SG were involved in 147 defining intellectual content, literature search, data acquisition, data analysis, statistical 148 analysis, manuscript preparation, manuscript editing, and manuscript review of the article. 149 All authors approved the final version of the manuscript. 150 151 References 152 1. Wulf HF. The centennial of spinal anesthesia. Anesthesiology. 1998;89:500–6. 153 2. Panditrao MM, Panditrao MM, Sunilkumar V, Panditrao AM. Effect of previous scorpion 154 bite(s) on the action of intrathecal bupivacaine: A case control study. Indian J Anaesth. 2013 155 May;57(3):236-40. 156 3. Panditrao MM, Panditrao MM, Khan MI, Yadav N. Does scorpion bite lead to development 157 of resistance to the effect of local anaesthetics? Indian J Anaesth. 2012 Nov;56(6):575-8. 158 4. McClure JH. Ropivacaine. Br J Anaesth. 1996;76:300–7. 159 5. Fettes PD, Hocking G, Peterson MK, Luck JF, Wildsmith JA. Comparison of plain and 160 hyperbaric solutions of ropivacaine for spinal anaesthesia. Br J Anaesth 2005;94:107-11. 161 6. Isbister G. K., Bawaskar H. S. Scorpion envenomation. The New England journal of 162 medicine 2014, 371(5), 457–463. 163 7. Craig D, Carli F. Bromage motor blockade score - a score that has lasted more than a lifetime. 164 Can J Anaesth. 2018 Jul;65(7):837-838. 165 8. Agrawal A, Kumar A, Consul S, Yadav A. Scorpion bite, a sting to the heart, Indian J Crit 166 Care Med. 2015 Apr;19(4):233-6. 167 9. Catterall WA, Cestèle S, Yarov-Yarovoy V, Yu FH, Konoki K, Scheuer T. Voltage-gated 168 ion channels and gating modifier toxins. Toxicon. 2007 Feb;49(2):124–41. 169 10. Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. Molecular determinants of state-170 dependent block of Na+ channels by local anesthetics. Science. 1994 Sep 16;265(5179):1724–171 8. 172 11. Rath A, Reena R. Scorpion bite and failed spinal anesthesia: is ropivacaine the answer? 173 Minerva Anestesiol. 2023 Apr;89(4):368-369. doi: 10.23736/S0375-9393.22.16958-0. 174 12. Lipkind GM, Fozzard HA. Molecular modeling of local anesthetic drug binding by 175 voltage-gated sodium channels. Mol Pharmacol. 2005 Dec;68(6):1611–22. 176 13. Li W, Ding L, Liu HM, You Q. Synthesis, biological evaluation, and molecular docking 177 of ropivacaine analogs as local anesthetic agents. Med Chem Res. 2018 Mar 1;27(3):954–65. 178 14. Yang Y, Si JQ, Fan C, Ma KT, Cheng HJ, Li L. Effects of ropivacaine on GABA-179 activated currents in isolated dorsal root ganglion neurons in rats, Chin. J Appl Physiol 2013 180 May;29(3):263-6. 181 15. Zhang L, Tanabe K, Yanagidate F, Kawasaki Y, Chen G, Dohi S, et al. Different effects 182 of local anesthetics on extracellular signal-regulated kinase phosphorylation in rat dorsal horn 183 neurons. Eur J Pharmacol. 2014 Jul 5;734:132-6. 184 185 Table 1: Demographic profile & Block parameters 186 Age (years) Gender ASA- PS Surgery Number of times of Scorpion sting Number of stings in past 5 years Duration since last sting (months) Severity of sting with Clinical Grade Sensory blockage Onset / Completion (seconds) Motor blockage Onset / Completion (seconds) 38 Female 1 Fistulect omy 1 1 48 Mild / 1 80 / 135 85 / 140 62 Male 2 Right inguinal hernia repair 1 1 42 Mild /1 65 / 90 82 / 120 38 Male 1 Left femur external fixation 3 2 4 Mild /1 56 / 82 72 / 110 70 Female 2 Right Proxima l Femur Nailing 1 1 12 Mild /1 39 / 50 55 / 67 58 Male 2 Right inguinal hernia repair 6 3 18 Moderate /2 94 / 140 70 / 166 26 Male 1 Left inguinal hernia repair 1 1 16 Mild /1 46 / 68 48 / 70 56 Male 2 Rt inguinal hernia repair 1 1 44 Mild /1 72 / 90 80 / 120 50 Male 1 End to end urethrop lasty 6 3 48 Severe / 3 135 / 175 155 / 190 56 Male 2 Right Inguinal hernia repair 2 2 22 Moderate /2 115 / 140 125 / 190 55 Male 2 Right Inguinal hernia repair 4 2 48 Moderate /2 90 / 200 130 / 294 ASA-PS – American Society of Anesthesiologists Physical Status. 187 188 189 Figure 1: A) Association between Number of Scorpion Stings and Mean block Time, B) 190 Association between Duration since last Scorpion Sting and Mean block Time, C) Association 191 between Clinical Severity Grade of Scorpion Sting and Mean block Time. 192 193 6 0 .4 8 7 1 1 4 .5 7 0 1 0 9 1 1 2 .5 8 6 .6 1 4 0 .6 1 5 7 .5 1 0 3 .4 1 9 8 1 7 8 1 S T I N G 2 T O 5 S T I N G S > 5 S T I N G S M E A N T IM E ( S E C O N D S ) NUMBER OF SCORPION STING ( A ) A S S O C I A T I O N B E T W E E N N U M B E R O F S T I N G S & M E A N B L O C K T I M E 5 6 7 2 .5 8 8 .4 8 2 9 9 .5 1 3 8 7 2 8 4 .5 1 0 6 .4 1 1 0 1 2 3 .2 5 1 7 2 .8 < 1 2 M O N T H S 1 2 T O 2 4 M O N T H S 2 4 T O 4 8 M O N T H S M E A N T IM E ( S E C O N D S ) DURATION SINCE LAST STING ( B ) A S S O C I A T I O N B E T W E E N T I M E S I N C E L A S T S T I N G & M E A N B L O C K T I M E 5 9 .6 7 1 0 2 .5 1 1 2 .5 8 5 .8 3 1 7 0 1 5 7 .5 7 0 .3 3 1 2 7 .5 1 3 2 .5 1 0 4 .5 0 2 4 2 1 7 8 1 2 3 M E A N T IM E ( S E C O N D S ) CLINICAL SEVERITY GRADES OF SCORPION STING ( C ) A S S O C I A T I O N B E T W E E N S E V E R I T Y G R A D I N G O F S C O R P I O N S T I N G & M E A N B L O C K T I M E Sensory Blockage Onset time (seconds) Sensory Blockage Completion time (seconds) Motor Blockage Onet time (seconds) Motor Blockage Completion time (seconds) 194 Figure 2: Variation of Mean Arterial Pressure with time in each patient. 195