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 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 » Conclusion
 »  References
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DRUG WATCH
Year : 2021  |  Volume : 53  |  Issue : 2  |  Page : 153-156
 

Ropivacaine induced systemic toxicity in a patient with phacomatosis pigmentokeratotica


Department of Anesthesia, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission25-Jul-2020
Date of Decision25-Sep-2020
Date of Acceptance30-Apr-2021
Date of Web Publication26-May-2021

Correspondence Address:
Dr. Tanvir Samra
Department of Anesthesia, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.IJP_521_20

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 » Abstract 


Calculation of the maximum recommended dose of local anesthetic minimizes the risk of Local Anesthetic Systemic Toxicity (LAST) when administrating multiple blocks for lower limb surgeries. Ropivacaine is the preferred local anesthetic as it is less lipophilic than bupivacaine and thus results in less central nervous system (CNS) and cardiovascular toxicity. The presence of developmental, congenital, and metabolic disorders mandates an extracautious approach in the administration of large volume of Local anaesthesia (LA) as the vascularity of the limb, levels of alpha-1-acid glycoprotein, and sensitivity of the sodium channels may be altered. This case report highlights successful resuscitation of a patient with Phacomatosis pigmentokeratotica after the development of CNS toxicity secondary to the administration of ropivacaine in ultrasound-guided combined lumbar plexus and sciatic nerve block. We identified some high risk patient profiles which should be vigilantly monitored to minimize the incidence of LAST.


Keywords: Bupivacaine, lidocaine, lipid emulsion, local anesthetic, phacomatosis pigmentokeratotica, ropivacaine


How to cite this article:
Aditya A, Amar P, Chander A, Goel N, Jain K, Samra T. Ropivacaine induced systemic toxicity in a patient with phacomatosis pigmentokeratotica. Indian J Pharmacol 2021;53:153-6

How to cite this URL:
Aditya A, Amar P, Chander A, Goel N, Jain K, Samra T. Ropivacaine induced systemic toxicity in a patient with phacomatosis pigmentokeratotica. Indian J Pharmacol [serial online] 2021 [cited 2021 Jun 15];53:153-6. Available from: https://www.ijp-online.com/text.asp?2021/53/2/153/316954





 » Introduction Top


Orthopedic lower limb surgeries are generally performed using regional anesthesia or central neuraxial blockade. Some limitations with the later are unpredictable level of block, epidural hematoma, urinary retention, prolonged sympathetic block, and delayed postoperative recovery.[1] Hence, peripheral nerve blocks are gaining popularity.

One of the main consideration while administrating local anesthetics in the sciatic nerve and lumbar plexus is to limit the total volume of the drug so that the total permissible dose which is 3 mg.kg − 1 for ropivacaine is not exceeded.[2] In the Indian scenario, we usually get patients with low body weight, and thus, the value of this dose is very low.

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome with sebaceous differentiation. The characterization of speckled lentiginous nevus is papular and is associated with extracutaneous anomalies namely neurological, ophthalmological and skeletal.[3] There is no data available on anaesthetic management of patients with PPK. The pharmacodynamic and pharmacokinetic relationship of the anesthestic drugs and their side effects are unknown. We report the occurrence of local anesthetic systemic toxicity (LAST) in a patient with PPK administered ropivacaine for ultrasound-guided combined lumbar plexus-sciatic nerve block.


 » Case Report Top


A 22-year-old, 63 kg male patient, with right-sided PPK [Figure 1] was scheduled for a fascio-cutaneous flap for a nonunion of the tibia with a gaping wound in the left lower limb. The patient had been reviewed a day prior in the preanesthetic clinic and had no comorbid conditions or significant history, thus classified as American Society of Anesthesiologists physical status Class I. After confirming nil per oral status, patient was wheeled in to the operating room and standard monitoring was used. An ultrasound-guided lumbar plexus block was given using Shamrock technique. Sciatic nerve was visualized using the subgluteal approach and an artery was identified near to it, which was confirmed on Doppler [Figure 2]. It was carefully avoided during insertion of the insulated nerve block needle. A nerve stimulator was also used along with ultrasound to increase success of the blocks. The calculated permissible dose of ropivacaine for the patients was 189 mg (3 mg.kg − 1) and we administered a total of 35 ml of 0.5% ropivacaine for combined lumbar plexus and sciatic nerve block; 20 ml of 0.5% (100 mg) for left lumbar-plexus block and 15 ml of 0.5% (75 mg) for left sciatic nerve block.
Figure 1: Patient with right-sided Phacomatosis pigmentokeratotica

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Figure 2: Sono-anatomy of sub-gluteal approach with biphasic waveform of artery near sciatic nerve. IT = Ischial tuberosity, GMM = Glutius maximus muscle, SN = Sciatic nerve, QFM = Quadratus femoris muscle

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Immediately after the completion of the block and positioning the patient supine, an episode of generalized tonic–clonic seizure (GTCS) occurred. Inj. Midazolam 3 mg was given intravenously and 100% oxygen was administered. The patient had another episode of GTCS, followed by apnea for which endotracheal intubation was done. In view of the chronology of events, we suspected LAST and a loading dose of 95 ml (1.5 ml.kg − 1) of intralipid emulsion (ILE) was administered over a minute followed by an infusion at the rate of 15 ml.kg.h − 1. A total of 600 ml of ILE was administered, and the patient was observed for any signs of deterioration. As there was no arrhythmia or significant hemodynamic alteration throughout the course of monitoring, intralipid was discontinued.

The patient was extubated after gaining consciousness and return of adequate spontaneous breathing efforts after an interval of 1 h. Surgery was abandoned, and the patient shifted out of operation theater with regular spontaneous respiration, stable vitals (with 88 bpm heart rate, 110/66 mmHg of blood pressure, and 100% saturation in pulse oximetry) with no complaints of perioral numbness or body ache.

The patient was observed for next 48 h. Electroencephalogram and noncontrast computed tomography (CT) scan of the brain were normal. After an interval of 2 weeks, the surgery was done under general anesthesia with uneventful recovery.


 » Discussion Top


Underlying mechanism of LAST is multifactorial, and the clinical presentation varies from prodromal symptoms, (dizziness, tinnitus, perioral numbness, agitation, and confusion) to respiratory failure, seizures, palpitations, arrhythmias, or asystole.[4] It is acute in onset and is reported immediately after injection of LA, but the recent data have shown delayed presentation too.[5],[6] Central nervous system (CNS) toxicity in the form of seizures is the most common presenting feature of LAST, and in this case too, the features of CNS toxicity appeared immediately after the administration of both the blocks.

LAST with ropivacaine is rare, and in this case report, two plausible yet divergent explanations for the occurrence of this adverse effect exist; co-incidental occurrence of LAST in a patient with PPK or increased susceptibility to LAST due to PPK.

Coincidental occurrence can be explained by

  1. Accidental intravascular injection of the LA: Negative aspiration was confirmed after every 3 ml of injected drug. However, the likelihood of inadvertent intravascular injection cannot be neglected completely as there is an ~2% false-negative rate for this diagnostic intervention[7]
  2. Plasma absorption of clinically acceptable doses: In the present case, the total dose given was 175 mg of ropivacaine, which was lower than the maximum allowed dose of 189 mg (3 mg/kg), for a 63 kg adult, but case reports of neurotoxicity at clinical doses exist.[8],[9] The minimum plasma concentration above which the incidence of CNS toxicity increases is dependent on the rate of increase in plasma concentration.[10] This implies that a permissible dose if injected at a fast rate increases the risk of LAST. Vanterpool et al. demonstrated that the total plasma ropivacaine concentration rises more quickly when sciatic nerve block is coadministered with lumbar plexus block.[11]


Increased susceptibility to LAST due to PPK needs to be further investigated as the pharmacokinetic and pharmacodynamic differences owing to the disease have not been extensively studied, and no evidence exists to establish causality in this case. Extracutaneous vascular malformations in patients with PPK exist and increased vascularity is known to increase plasma concentrations, but we did not perform contrast-enhanced CT scan to prove the same in our case.[12] The authors found a pulsatile vessel in the proximity of sciatic nerve, which was confirmed to be an artery on Doppler [Figure 2]. Whether these vessels present in the sub-gluteal space were the branches of the inferior gluteal vessels, sciatic nerve vein or the branch of the medial circumflex femoral artery or vascular malformations is an uninvestigated sonographic finding in our case.[13] Plasma concentrations of ropivacaine were not monitored due to unavailability of laboratory service for the same thus hindering the formulation of a causative etiology. However, the need to adopt an extracautious approach in the administration of large volume of LA due to the added complexity of the disease in this subset of patients needs to be remembered.

LA are lipophillic, thus ILE acts as a lipid sink and can shunt LA from high blood flow organ such as brain and heart to storage or detoxification organs such as muscle and liver.[14] The AAGBI recommended ILE regimen following cardiac arrest from LAST.[15] The role of ILE is not clear for patients with purely neurological sign, but early administration of ILE can attenuate neurological manifestations and prevent clinical deterioration and progression to cardiovascular system arrest. Thus, we used it in our case.


 » Conclusion Top


Risk factors that increase the incidence of LAST need to be identified in every patient being considered for high volume dual peripheral nerve blocks. Dose reduction is recommended when repeated intermittent boluses or continuous infusions of LA are planned in patients with coexisting cardiac, renal, or hepatic disease.[16] The susceptibility of patients to LA-induced myocardial depression and arrhythmogenic potential is enhanced in the presence of severe cardiac dysfunction due to hypoperfusion of the hepatic and renal vascular beds translating into a reduction in metabolism and elimination, respectively. Dose reduction is recommended in severe heart failure. Parturients and patients at the extremes of age and with reduced skeletal muscle mass are candidates for dose reduction of 10%–20%. Experimental research to study pharmacodynamics and pharmacokinetics of local anesthetics in patients with developmental, congenital, and metabolic disorders need to be conducted. Till then, central neuraxial blocks to be preferred over regional nerve blocks on the pretext that the absorption of LA into the systemic circulation are slow after epidural administration.[17]

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Horlocker TT. Peripheral nerve blocks – Regional anesthesia for the new millennium. Reg Anesth Pain Med 1998;23:237-40.  Back to cited text no. 1
    
2.
McClellan KJ, Faulds D. Ropivacaine: An update of its use in regional anaesthesia. Drugs 2000;60:1065-93.  Back to cited text no. 2
    
3.
Happle R, Hoffmann R, Restano L, Caputo R, Tadini G. Phacomatosis pigmentokeratotica: A melanocytic-epidermal twin nevus syndrome. Am J Med Genet 1996;65:363-5.  Back to cited text no. 3
    
4.
Mercado P, Weinberg GL. Local anesthetic systemic toxicity: Prevention and treatment. Anesthesiol Clin 2011;29:233-42.  Back to cited text no. 4
    
5.
Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: Incidence and preventive measures. Reg Anesth Pain Med 2002;27:556-61.  Back to cited text no. 5
    
6.
Kang HY, Kim JE, Kim YJ, Park SW, Kim Y. An unusual delayed onset of systemic toxicity after fluoroscopy-guided cervical epidural steroid injection with levobupivacaine: A case report. Pain Pract 2019;19:762-6.  Back to cited text no. 6
    
7.
Neal JM, Barrington MJ, Fettiplace MR, Gitman M, Memtsoudis SG, Mörwald EE, et al. The third American Society of regional anesthesia and pain medicine practice advisory on local anesthetic systemic toxicity: Executive summary 2017. Reg Anesth Pain Med 2018;43:113-23.  Back to cited text no. 7
    
8.
Satsumae T, Tanaka M, Saito S, Inomata S. Convulsions after ropivacaine 300 mg for brachial plexus block. Br J Anaesth 2008;101:860-2.  Back to cited text no. 8
    
9.
Dhir S, Ganapathy S, Lindsay P, Athwal GS. Case report: Ropivacaine neurotoxicity at clinical doses in interscalene brachial plexus block. Can J Anaesth 2007;54:912-6.  Back to cited text no. 9
    
10.
Stoelting RK. Local anesthetics. In: Stoelting RK, editor. Pharmacology and Physiology in Anesthetic Practice. 4th ed. Philadelphia:Lippincott Williams and Wilkins; 2006. p. 179-207.  Back to cited text no. 10
    
11.
Vanterpool S, Steele SM, Nielsen KC, Tucker M, Klein SM. Combined lumbar-plexus and sciatic-nerve blocks: An analysis of plasma ropivacaine concentrations. Reg Anesth Pain Med 2006;31:417-21.  Back to cited text no. 11
    
12.
Boente Mdel C, Asial RA, Happle R. Phacomatosis pigmentokeratotica: A follow-up report documenting additional cutaneous and extracutaneous anomalies. Pediatr Dermatol 2008;25:76-80.  Back to cited text no. 12
    
13.
Guardini R, Waldron BA, Wallace WA. Sciatic nerve block: A new lateral approach. Acta Anaesthesiol Scand 1985;29:515-9.  Back to cited text no. 13
    
14.
Fettiplace MR, Lis K, Ripper R, Kowal K, Pichurko A, Vitello D, et al. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release 2015;198:62-70.  Back to cited text no. 14
    
15.
AAGBI, Management of Severe Local Anaesthetic Toxicity, AAGBI Safety Guideline; 2010. Available from: http://www.aagbi.org/publications/guidelines/docs/latoxicity 2010.pdf. [Last accessed 2020 Apr 22].  Back to cited text no. 15
    
16.
El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: Current perspectives. Local Reg Anesth 2018;11:35-44.  Back to cited text no. 16
    
17.
Cusato M, Allegri M, Niebel T, Ingelmo P, Broglia M, Braschi A, et al. Flip-flop kinetics of ropivacaine during continuous epidural infusion influences its accumulation rate. Eur J Clin Pharmacol 2011;67:399-406.  Back to cited text no. 17
    


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