Clinical trial NCT03731429: Lidocaine to Prevent Cough and Hemodynamic Changes in Tracheal Extubation
Official title: Efficiency of Intravenous Lidocaine to Reduce Coughing and the Hemodynamic Changes Associated to Tracheal Extubation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Lidocaine
Keywords: Cough
Sore throat
Hemodynamic changes
Extubation
Lidocaine
Double blind
Lead sponsor: Hospital Fernandez
Sponsor class: OTHER
First posted: 2018-11-06
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study was designed as a double-blind randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Coughing during tracheal extubation can be associated to adverse effects like tachycardia, arterial hypertension (AHT), increase of intracranial pressure (ICP) and intraocular pressure (IOP), and the dehiscence of surgical wounds. In ophthalmic, head and neck, and abdominal surgery, and in several other neurosurgical interventions it is vital to prevent these effects. The incidence of laryngeal irritation due to orotracheal intubation hinders patient comfort in the immediate postoperative (POP) period and no pharmacological intervention has been yet proven to prevent it.

At the end of the surgical procedure, the depth of the anesthetic plane decreases with the concomitant suspension of the anesthetic agents. However, the patient still requires ventilatory support through the endotracheal tube (EDT). The physical stimulation of the trachea created by this foreign body leads to the activation of the sympathetic nervous system, expressed in AHT, tachycardia, and ICP. To tolerate the EDT and prevent these effects, different maneuvers have been tested such as extubating the patient in a deep anesthetic plane or administering intravenous (IV) narcotics with the entailed complications: airway (AW) obstruction and hypercapnia, and the aspiration of an unprotected AW. Progress has been made with the introduction of ultrashort acting opioids, with significant statistical results. Moreover, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors and dexmedetomidine have been used to decrease the hemodynamic impact associated to tracheal extubation. The use of both IV and intratracheal lidocaine in doses ranging from 1 mg/kg to 3 mg/kg, has been studied with controversial results.

In view of the above, and as lidocaine is the most commonly used low-cost drug in all operating rooms with a good safety profile when used at low doses, the purpose of this study is twofold: to assess its effects at reducing coughing and to evaluate its hemodynamic impact when administering IV 1 mg/kg prior to extubation. Then, the efficiency of reducing the incidence of sore throats after the immediate POP shall be investigated.


Eligibility criteria: Inclusion criteria:

* American Society of Anesthesiologists Risk I \& II.
* Age 18-65 years.
* Scheduled for: cholecystectomy, hernioplasty or laparoscopic gynecological surgery, under balanced general anesthesia (GA) and orotracheal intubation (OTI).

Exclusion criteria:

* Local anesthetic (LA) allergy.
* Presence of predictors of potentially difficult intubation (DI) according to criteria defined by the American Society of Anesthesiologists.
* Upper airway inflammatory symptoms during the previous week.
* Chronic kidney disease with clearance lower than 60 ml/m using the Modification of Diet in Renal Disease (MDRD) equation.
* Child-Pugh B-C liver disease.
* Treated with ACEinhibitors and/or BB.
* Second and third grade atrioventricular block.
* Symptomatic bradycardia.
* Tachyarrhythmias.
* Left bundle branch block (LBBB).

Primary outcomes:
measure: Determine the efficiency of IV lidocaine in reducing the incidence of coughing
timeFrame: From the moment the endotracheal tube is retired to 5 minutes after
measure: Determine the efficiency of IV lidocaine in reducing the arterial hypertension associated with tracheal extubation
timeFrame: From the end of anesthesia to 5 minutes after tracheal extubation (At time 0, time 2 and time 3)
measure: Determine the efficiency of IV lidocaine in reducing the increase in heart rate (HR) associated with tracheal extubation
timeFrame: From the end of anesthesia to 5 minutes after tracheal extubation (At time 0, time 2 and time 3)
Secondary outcomes:
measure: Record the time elapsed from the end of anesthesia and the administration of lidocaine to extubation.
timeFrame: Intraoperative. From the end of anesthesia (time 0) to tracheal extubation (time 2)
measure: Assess immediate POP sore throat
timeFrame: 30 minutes after extubation
Other outcomes:
measure: Monitor the adverse reactions (AR) that may occur after the administration of IV lidocaine and report them
timeFrame: 24 hours after extubation
Locations:
city: Capital federal
country: Argentina
facility: Hospital Fernandez
state: Buenos Aires
Study officials:
affiliation: Hospital Fernandez
name: Santiago Ficcadenti, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Minogue SC, Ralph J, Lampa MJ. Laryngotracheal topicalization with lidocaine before intubation decreases the incidence of coughing on emergence from general anesthesia. Anesth Analg. 2004 Oct;99(4):1253-1257. doi: 10.1213/01.ANE.0000132779.27085.52.
citation: Hohlrieder M, Tiefenthaler W, Klaus H, Gabl M, Kavakebi P, Keller C, Benzer A. Effect of total intravenous anaesthesia and balanced anaesthesia on the frequency of coughing during emergence from the anaesthesia. Br J Anaesth. 2007 Oct;99(4):587-91. doi: 10.1093/bja/aem203. Epub 2007 Jul 27.
citation: Bruder N, Pellissier D, Grillot P, Gouin F. Cerebral hyperemia during recovery from general anesthesia in neurosurgical patients. Anesth Analg. 2002 Mar;94(3):650-4; table of contents. doi: 10.1097/00000539-200203000-00031.
citation: Coles JP, Leary TS, Monteiro JN, Brazier P, Summors A, Doyle P, Matta BF, Gupta AK. Propofol anesthesia for craniotomy: a double-blind comparison of remifentanil, alfentanil, and fentanyl. J Neurosurg Anesthesiol. 2000 Jan;12(1):15-20. doi: 10.1097/00008506-200001000-00004.
citation: Talke P, Caldwell JE, Brown R, Dodson B, Howley J, Richardson CA. A comparison of three anesthetic techniques in patients undergoing craniotomy for supratentorial intracranial surgery. Anesth Analg. 2002 Aug;95(2):430-5, table of contents. doi: 10.1097/00000539-200208000-00036.
citation: Christensen AM, Willemoes-Larsen H, Lundby L, Jakobsen KB. Postoperative throat complaints after tracheal intubation. Br J Anaesth. 1994 Dec;73(6):786-7. doi: 10.1093/bja/73.6.786.
citation: Harding CJ, McVey FK. Interview method affects incidence of postoperative sore throat. Anaesthesia. 1987 Oct;42(10):1104-7. doi: 10.1111/j.1365-2044.1987.tb05179.x.
citation: Herlevsen P, Bredahl C, Hindsholm K, Kruhoffer PK. Prophylactic laryngo-tracheal aerosolized lidocaine against postoperative sore throat. Acta Anaesthesiol Scand. 1992 Aug;36(6):505-7. doi: 10.1111/j.1399-6576.1992.tb03507.x.
citation: Lee B, Lee JR, Na S. Targeting smooth emergence: the effect site concentration of remifentanil for preventing cough during emergence during propofol-remifentanil anaesthesia for thyroid surgery. Br J Anaesth. 2009 Jun;102(6):775-8. doi: 10.1093/bja/aep090. Epub 2009 May 2.
citation: Mayhan WG. Disruption of blood-brain barrier during acute hypertension in adult and aged rats. Am J Physiol. 1990 Jun;258(6 Pt 2):H1735-8. doi: 10.1152/ajpheart.1990.258.6.H1735.
citation: Gauthier A, Girard F, Boudreault D, Ruel M, Todorov A. Sevoflurane provides faster recovery and postoperative neurological assessment than isoflurane in long-duration neurosurgical cases. Anesth Analg. 2002 Nov;95(5):1384-8, table of contents. doi: 10.1097/00000539-200211000-00052.
citation: Lowrie A, Johnston PL, Fell D, Robinson SL. Cardiovascular and plasma catecholamine responses at tracheal extubation. Br J Anaesth. 1992 Mar;68(3):261-3. doi: 10.1093/bja/68.3.261.
citation: Grillo P, Bruder N, Auquier P, Pellissier D, Gouin F. Esmolol blunts the cerebral blood flow velocity increase during emergence from anesthesia in neurosurgical patients. Anesth Analg. 2003 Apr;96(4):1145-1149. doi: 10.1213/01.ANE.0000055647.54957.77.
citation: Muzzi DA, Black S, Losasso TJ, Cucchiara RF. Labetalol and esmolol in the control of hypertension after intracranial surgery. Anesth Analg. 1990 Jan;70(1):68-71.
citation: Fujii Y, Saitoh Y, Takahashi S, Toyooka H. Combined diltiazem and lidocaine reduces cardiovascular responses to tracheal extubation and anesthesia emergence in hypertensive patients. Can J Anaesth. 1999 Oct;46(10):952-6. doi: 10.1007/BF03013130.
citation: Tsutsui T. Combined administration of diltiazem and nicardipine attenuates hypertensive responses to emergence and extubation. J Neurosurg Anesthesiol. 2002 Apr;14(2):89-95. doi: 10.1097/00008506-200204000-00001.
citation: Kross RA, Ferri E, Leung D, Pratila M, Broad C, Veronesi M, Melendez JA. A comparative study between a calcium channel blocker (Nicardipine) and a combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension during craniotomy for tumor surgery. Anesth Analg. 2000 Oct;91(4):904-9. doi: 10.1097/00000539-200010000-00024.
citation: Tanskanen PE, Kytta JV, Randell TT, Aantaa RE. Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumour surgery: a double-blind, randomized and placebo-controlled study. Br J Anaesth. 2006 Nov;97(5):658-65. doi: 10.1093/bja/ael220. Epub 2006 Aug 16.
citation: Nho JS, Lee SY, Kang JM, Kim MC, Choi YK, Shin OY, Kim DS, Kwon MI. Effects of maintaining a remifentanil infusion on the recovery profiles during emergence from anaesthesia and tracheal extubation. Br J Anaesth. 2009 Dec;103(6):817-21. doi: 10.1093/bja/aep307. Epub 2009 Oct 28.
citation: Shajar MA, Thompson JP, Hall AP, Leslie NA, Fox AJ. Effect of a remifentanil bolus dose on the cardiovascular response to emergence from anaesthesia and tracheal extubation. Br J Anaesth. 1999 Oct;83(4):654-6. doi: 10.1093/bja/83.4.654.
citation: Ghodraty MR, Hasani V, Bagheri-Aghdam A, Zamani MM, Pournajafian A, Rokhtabnak F, Kholdebarin A, Nader ND. Remifentanil infusion during emergence moderates hemodynamic and cough responses to the tracheal tube: A randomized controlled trial. J Clin Anesth. 2016 Sep;33:514-20. doi: 10.1016/j.jclinane.2015.09.001. Epub 2015 Oct 23.
citation: Altintas F, Bozkurt P, Kaya G, Akkan G. Lidocaine 10% in the endotracheal tube cuff: blood concentrations, haemodynamic and clinical effects. Eur J Anaesthesiol. 2000 Jul;17(7):436-42. doi: 10.1046/j.1365-2346.2000.00696.x.
citation: Prengel AW, Lindner KH, Hahnel JH, Georgieff M. Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration. Anesth Analg. 1993 Nov;77(5):985-9. doi: 10.1213/00000539-199311000-00019.
citation: Baraka A. Intravenous lidocaine controls extubation laryngospasm in children. Anesth Analg. 1978 Jul-Aug;57(4):506-7. doi: 10.1213/00000539-197807000-00028. No abstract available.
citation: Bidwai AV, Bidwai VA, Rogers CR, Stanley TH. Blood-pressure and pulse-rate responses to endotracheal extubation with and without prior injection of lidocaine. Anesthesiology. 1979 Aug;51(2):171-3. doi: 10.1097/00000542-197908000-00020. No abstract available.
citation: Copeland SE, Ladd LA, Gu XQ, Mather LE. The effects of general anesthesia on whole body and regional pharmacokinetics of local anesthetics at toxic doses. Anesth Analg. 2008 May;106(5):1440-9, table of contents. doi: 10.1213/ane.0b013e31816ba541.
citation: Copeland SE, Ladd LA, Gu XQ, Mather LE. The effects of general anesthesia on the central nervous and cardiovascular system toxicity of local anesthetics. Anesth Analg. 2008 May;106(5):1429-39, table of contents. doi: 10.1213/ane.0b013e31816d12af.
citation: Shankar Ramaswamy, John A. Wilson, Lesley Colvin. Non-opioid-based adjuvant analgesia in perioperative care. Continuing Education in Anaesthesia, Critical Care & Pain. 2013; 13:152-7.
citation: N Eipe, S Gupta, J Penning. Intravenous lidocaine for acute pain: an evidence-based clinical update. Br J Anaesth Education. 2016; 16:292-8.
citation: Mazzone SB, Undem BJ. Cough sensors. V. Pharmacological modulation of cough sensors. Handb Exp Pharmacol. 2009;(187):99-127. doi: 10.1007/978-3-540-79842-2_6.
citation: STEINHAUS JE, GASKIN L. A study of intravenous lidocaine as a suppressant of cough reflex. Anesthesiology. 1963 May-Jun;24:285-90. doi: 10.1097/00000542-196305000-00006. No abstract available.
citation: Martínez-Zúñiga JP, Lorenzo-Balderas, Silva-Escobedo JG. Lidocaine in low doses combining intravenous and endotracheal therapies: reduces incidence of coughing and hemodynamic changes during extubation. Rev Sanid Milit Mex. 2011; 65:95-8.
citation: Zamora Lozano J, Cruz Villasenor JA, Rodriguez Reyes J, Sanchez Rodriguez JP, Briones Corona G, Gallardo Alonso LA. [Comparison of topical, intravenous, and intracuff lidocaine for reducing coughing after extubation during emergence from general anesthesia]. Rev Esp Anestesiol Reanim. 2007 Dec;54(10):596-601. Spanish.
citation: Saghaei M, Reisinejad A, Soltani H. Prophylactic versus therapeutic administration of intravenous lidocaine for suppression of post-extubation cough following cataract surgery: a randomized double blind placebo controlled clinical trial. Acta Anaesthesiol Taiwan. 2005 Dec;43(4):205-9.
citation: Lee JH, Koo BN, Jeong JJ, Kim HS, Lee JR. Differential effects of lidocaine and remifentanil on response to the tracheal tube during emergence from general anaesthesia. Br J Anaesth. 2011 Mar;106(3):410-5. doi: 10.1093/bja/aeq396. Epub 2011 Jan 2.
citation: Williams KA, Barker GL, Harwood RJ, Woodall NM. Combined nebulization and spray-as-you-go topical local anaesthesia of the airway. Br J Anaesth. 2005 Oct;95(4):549-53. doi: 10.1093/bja/aei202. Epub 2005 Aug 26.
citation: Mainland PA, Kong AS, Chung DC, Chan CH, Lai CK. Absorption of lidocaine during aspiration anesthesia of the airway. J Clin Anesth. 2001 Sep;13(6):440-6. doi: 10.1016/s0952-8180(01)00298-7.
citation: Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):564-75; discussion 524. doi: 10.1016/j.rapm.2004.08.003.
citation: Donald MJ, Derbyshire S. Lignocaine toxicity; a complication of local anaesthesia administered in the community. Emerg Med J. 2004 Mar;21(2):249-50. doi: 10.1136/emj.2003.008730.
citation: Scuderi PE. Postoperative sore throat: more answers than questions. Anesth Analg. 2010 Oct;111(4):831-2. doi: 10.1213/ANE.0b013e3181ee85c7. No abstract available.
citation: Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997 Jan;86(1):10-23. doi: 10.1097/00000542-199701000-00004.
citation: Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology. 1997 Jan;86(1):24-33. doi: 10.1097/00000542-199701000-00005.
citation: Kapila A, Glass PS, Jacobs JR, Muir KT, Hermann DJ, Shiraishi M, Howell S, Smith RL. Measured context-sensitive half-times of remifentanil and alfentanil. Anesthesiology. 1995 Nov;83(5):968-75. doi: 10.1097/00000542-199511000-00009.
citation: Burkle H, Dunbar S, Van Aken H. Remifentanil: a novel, short-acting, mu-opioid. Anesth Analg. 1996 Sep;83(3):646-51. doi: 10.1097/00000539-199609000-00038.
citation: Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993 Nov;79(5):881-92. doi: 10.1097/00000542-199311000-00004.
citation: Kim H, Min KT, Lee JR, Ha SH, Lee WK, Seo JH, Choi SH. Comparison of Dexmedetomidine and Remifentanil on Airway Reflex and Hemodynamic Changes during Recovery after Craniotomy. Yonsei Med J. 2016 Jul;57(4):980-6. doi: 10.3349/ymj.2016.57.4.980.
citation: Ikeda Y, Oda Y, Nakamura T, Takahashi R, Miyake W, Hase I, Asada A. Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats. Anesthesiology. 2010 Jun;112(6):1396-403. doi: 10.1097/ALN.0b013e3181d9cc54.