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Journal of Obstrectic Anaesthesia and Critical Care
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Year : 2023  |  Volume : 13  |  Issue : 1  |  Page : 109-111

Apparent acquired resistance to local anesthetics in a pregnant patient: Coincidence or a novel entity?—A Case report

Department of Anaesthesiology and Pain Medicine, Pt Jawaharlal Nehru Memorial Medical College and B. R. Ambedkar Hospital, Raipur, Chhattisgarh, India

Date of Submission25-Jun-2022
Date of Acceptance03-Oct-2022
Date of Web Publication09-Mar-2023

Correspondence Address:
Dr. Ayalasomayajula Sashank
Department of Anaesthesiology and Pain Medicine, Pt. Jawaharlal Nehru Memorial Medical College and B R Ambedkar Hospital, Jail Road, Opposite Central Jail, Moudhapara, Raipur - 492 001, Chhattisgarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JOACC.JOACC_39_22

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We present a case of a 28-year-old pregnant patient in labor with two prior cesarean sections with a history of both successful and failed spinal anesthesia in her first and second pregnancies, respectively. This time, attempts at spinal anesthesia failed twice despite ruling out the common causes such as technical or drug error. Surgery was ultimately performed under general anesthesia uneventfully. While technical factors may contribute substantially to failure of spinal anesthesia, the sequence of events in this case, viz. one successful subarachnoid block followed by two unsuccessful ones three and seven years apart, supported by investigative evidence, indicates a possible acquired resistance to local anesthetics.

Keywords: Acquired, case report, local anesthetics, pregnant, resistance

How to cite this article:
Jaya L, Sashank A, Sruthi K. Apparent acquired resistance to local anesthetics in a pregnant patient: Coincidence or a novel entity?—A Case report. J Obstet Anaesth Crit Care 2023;13:109-11

How to cite this URL:
Jaya L, Sashank A, Sruthi K. Apparent acquired resistance to local anesthetics in a pregnant patient: Coincidence or a novel entity?—A Case report. J Obstet Anaesth Crit Care [serial online] 2023 [cited 2023 Apr 1];13:109-11. Available from: https://www.joacc.com/text.asp?2023/13/1/109/371313

  Introduction Top

Throughout literature, there is just a smattering of reports (less than ten over last two decades[1],[2],[3],[4],[5],[6] of resistance to local anesthetics (LA) inside operation theatres), as this phenomenon is rarely encountered and even more difficult to diagnose. It is understandable then that such reports are greeted with skepticism and attributed to more likely etiologies like technical failure, drug failure,[2] or less clinician experience.[7] LA act by conduction blockade through sodium channels. Consequently, any aberrant response to their action may be a result of mutations in such channels.

We report a patient who presented for emergency cesarean section (CS). There was no sensorimotor block after initial and repeat subarachnoid block (SAB), despite evidence of accurate intervertebral space location and intrathecal drug administration. The patient recounted a similar experience in her previous pregnancy three years back when she had to be given general anesthesia (GA) for CS. Furthermore, she also gave history of a successful SAB during her first CS seven years ago. Although technical failure may contribute to failure of SAB in 4–13% cases,[8],[9] this peculiar history and clinical findings of differential success to SAB during three different surgeries at three different institutes many years apart suggest a true resistance to local anesthetics.

  Case History Top

A 28-year-old pregnant lady in labor, with no comorbidities and two previous CS, was scheduled for emergency CS. Her first CS was performed under SAB and second CS under GA after a failed SAB due to complete absence of sensorimotor block, at different institutes. Her preoperative anesthesia check-up (PAC) and laboratory results were within normal range. In view of one previously successful SAB and the well-documented failure rate of SAB due to various common etiologies such as technical or drug failure and unavailability of previous records of surgeries performed at different institutes, we decided to go ahead with SAB for this cesarean section. With the patient in sitting position, a 25-gauge Quincke's spinal needle was placed in the midline at L3-4 interspace. After attaining free flow of clear CSF, 10 mg of 0.5% hyperbaric bupivacaine was administered into the subarachnoid space.

The patient was placed supine, and sensory block to cold and pain sensation was evaluated. After ten minutes, no sensorimotor block was observed. After waiting for 20 minutes to exclude pseudo-failure, repeat spinal was given using a different interspace, viz. L4-5 with a different batch of 0.5% hyperbaric bupivacaine by a senior anesthesiologist. After ten minutes, again no sensorimotor blockade was observed. GA was given, and a healthy female baby was delivered with Apgar scores of 9 and 10 at 1 and 5 min, respectively. After the patient regained consciousness, absolutely no sensorimotor block was observed even after 90 minutes of SAB. MRI lumbosacral spine performed postoperatively was normal. Moreover, patient was detected to be non-hypoesthetic to both 2% lignocaine and 0.5% bupivacaine on intradermal testing.

  Discussion Top

Possible causes for failed spinal anesthetics include technical errors, medication failure, and abnormal distribution of local anesthetics.[2] Cases of failed spinal with confirmed subarachnoid injection have been reported. Wiskopf reported failure of a spinal catheter despite position confirmation both radiographically and manually by aspirating cerebrospinal fluid freely.[10] Bevacqua and Cleary reported anesthetic failure with hyperbaric lidocaine (total of 125 mg) given in two separate doses through a subarachnoid catheter.[11]

An extensive literature search did not throw up any cases of such drastic variant response to SAB for the same type of surgery in the same patient on different occasions many years apart, with no similar history in the family. As previously mentioned, technical or drug failure and clinician experience are possible causes for failure of SAB. However, in our case these factors were arguably mitigated by the triad of change of hands, change of intervertebral space (L3-4 to L4-5), and change of drug batch. Also, medication failure is usually an isolated incident and would not explain the conduct of successful SAB to other patients with the same lot of hyperbaric bupivacaine.

After eliminating the aforementioned common etiologies of spinal failure, we are forced to ponder if micromolecular defects such as local anesthetic receptor mutations and sodium channel abnormalities might appear to be a plausible explanation. A genetic variation in the amino acid sequence within the sodium channel might result in an inappropriate receptor site. Specifically, the sodium channel consists of alpha, beta-1, and beta-2 subunits. The alpha subunit involves four homologous domains (I–IV) each made up of six transmembrane segments (S1–S6). LA action is believed to be at sites involving phenylalanine and tyrosine amino acid residues, due to an interaction with the sixth segment of domain four of the alpha subunit (IV-S6). Mutations that alter this site of action might account for such cases of local anesthetic "resistance" or failure.[12] Such mutations may be congenital or acquired. Congenital mutations are inherited from parents and are present from birth, whereas acquired ones are picked up over a period of time during life. Clendenen N et al.[13] reported LA resistance in a family of three people by demonstrating a genetic variation in the sodium channel subunit (Nav1.5) present in the peripheral nerves, by exome sequencing. The fact that our patient was responsive to LA in her first CS but became unresponsive in subsequent CS many years apart, substantiated by an intradermal wheal test, likely points toward an acquired genetic variation, possibly local anesthetic resistance. A limitation in our case could be the lack of confirmation of the abovesaid entity by genetic analysis due to unavailability in our setup.

  Conclusion Top

In a case of unsuccessful SAB despite standard troubleshooting techniques mitigating technical or drug failure, and a normal lumbosacral spine imaging, compounded by a perplexing history of successful and failed spinals over many years, and a negative LA sensitivity test, acquired resistance to local anesthetics and not coincidence, emerges as the likely explanation for the observed clinical scenario.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Trescot AM. Local anaesthetic "resistance". Pain Physician 2003;6:291-3.  Back to cited text no. 1
Kavlock, R, Ting PH. Local anesthetic resistance in a pregnant patient with lumbosacral plexopathy. BMC Anesthesiology. 2004 4(1);1.  Back to cited text no. 2
Batas D, Nejad MRG, Prabhu PK. Resistance to Local Anaesthetics: a case report. British Journal of Anaesthesia. 2007: 99.  Back to cited text no. 3
Anand P, Kamath S, Yarmush J. (216) Failed regional anesthesia: local anesthetic resistance possibly due to voltage gated sodium channellopathy: A Case Report. The Journal of Pain: Official Journal of the American Pain Society. 2017:18(4).  Back to cited text no. 4
Schutte SS, Euliano T. Local anesthetic resistance in a Crohn's patient undergoing cesarean delivery. Reg Anesth Pain Med 2020;45:669-70.  Back to cited text no. 5
Marti F, Lindner G, Ravioli S. Resistance to local anaesthetics: A literature review. Br J Anaesth 2022;129:e43-5.  Back to cited text no. 6
Parikh KS, Seetharamaiah S. Approach to failed spinal anaesthesia for caesarean section. Indian J Anaesth 2018;62:691-7.  Back to cited text no. 7
[PUBMED]  [Full text]  
Munhall RS, Sukhani R, Winnie AP. Incidence and etiology of failed spinal anesthetics in a university hospital. Anesth Analg 1988;67:843-8.  Back to cited text no. 8
Levy JH, Ioles JA, Ghia JN, Turnbull C. A retrospective study of the incidence and causes of failed spinal anesthetics in a university hospital. Anesth Analg 1985;64:705-10.  Back to cited text no. 9
Weiskopf RB. Unexplained failure of a continuous spinal anesthetic. Anesthesiology 1970;33:114-6.  Back to cited text no. 10
Bevacqua BK, Cleary WF. Relative resistance to intrathecal local anesthetics. Anesth Analg 1994;78:1024-6.  Back to cited text no. 11
Ragsdale DS, McPhee JC, Scheuer T, Catterall WA. Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science 1994;265:1724-8.  Back to cited text no. 12
Clendenen N, Cannon AD, Porter S, Robards CB, Parker AS, Clendenen SR. Whole- exome sequencing of a family with local anesthetic resistance. Minerva Anestesiol 2016;82:1089-97.  Back to cited text no. 13


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