High Dose IV Lidocaine vs Hydromorphone for Abdominal Pain in the Emergency Department (HIDO-LIDO)

High Dose Intravenous Lidocaine vs Hydromorphone for Acute Abdominal Pain in the Emergency Department: A Randomized, Comparative Efficacy Trial

Intravenous lidocaine will be given at a dose of 2 mg/kg intravenously to patients in the emergency department with a diagnosis of acute abdominal pain. Its efficacy will be compared to 1 mg of intravenous hydromorphone, with a primary endpoint of mean improvement of pain at 90 minutes.

Study Overview

• Status: Terminated
• Conditions: Renal Colic; Abdominal Pain
• Intervention / Treatment: Drug: Lidocaine Iv; Drug: HYDROmorphone Injection

Detailed Description

Abdominal pain is a common chief complaint for patients presenting to the emergency department (ED) in the United States. Intravenous opioids are commonly used to treat acute abdominal pain in the ED. These medications are highly efficacious and, when used in a monitored setting such as the ED, extremely safe. Use of opioids has fallen out of favor because of a spike in opioid-related overdose deaths throughout the United States. While use of opioids in the ED is unlikely to contribute to outpatient opioid deaths, minimizing the use of opioids in the ED will contribute to an opioid free culture, in which opioids are used only when absolutely necessary. A variety of different types of medications can be used in lieu of opioids. One such medication, intravenous lidocaine, has been used extensively for neuropathic pain, in the peri- and post-operative surgical setting, the cardiac care unit, and most recently in the emergency department.

Intravenous lidocaine has long been used to treat pain. In publications dating back to 1980, intravenous lidocaine has been shown to be an effective treatment for neuropathic pain. In the postoperative setting, intravenous lidocaine decreased pain and decreased the need for opiates. More recently, emergency medicine investigators in Iran demonstrated that intravenous lidocaine decreased pain associated with renal colic and limb ischemia. An ED-based study in the United States showed comparable efficacy between morphine and intravenous lidocaine when used for acute pain. Most recently, a prospective RCT showed 120 mg of intravenous lidocaine was efficacious for abdominal pain, albeit not as effective as 1 mg of hydromorphone. However, a subgroup analysis showed that when lidocaine was dosed at 2 mg/kg, it was equally as effective as hydromorphone.

Over the years, intravenous lidocaine has been used for a variety of indications including arrhythmia prophylaxis in patients with acute coronary syndromes. Known side effects of intravenous lidocaine range from transient neurological symptoms (dizziness, paresthesias), to cardiac dysrhythmias and seizure. To date, no deaths have been attributed to its use for treating pain, and the only documented significant complication was due to an unintentional overdose when a patient received ten times the normal dose. All reported side effects in pain patients have been transient and resolved by either stopping the drug, decreasing the infusion rate or by observation alone. Additionally, doses of 2 mg/kg have been tolerated well in the outpatient setting, operating room and ED without any serious side effects. Thus, intravenous lidocaine is an emerging medication for safe and rapid relief of pain, has no known addictive properties, and creates a potential for a pain practice paradigm shift in the United States.

We therefore propose a randomized, double blind, comparative efficacy trial to address the following aim:

To determine if a 2 mg/kg dose of intravenous lidocaine is as equally efficacious as a single dose of 1 mg intravenous hydromorphone for acute abdominal pain in the emergency department.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be a patient in the emergency department (ED)
• Must have acute abdominal pain, defined as abdominal or flank pain of a duration of 7 days or less
• Predicted treatment must include the use of an intravenous opiate

Exclusion Criteria:

• Cardiac conduction system impairment (QTc duration > 0.5s, QRS duration > 0.12s, PR interval <0.12s or > 0.2s)
• Known renal (CKD >2) or liver disease (Childs-Pugh B or greater)
• Hemodynamically instability, defined by the attending physician
• Pregnant or breastfeeding
• Have a known allergy to either medication
• Used of prescription or illicit opioids within the previous week
• Patients with a chronic pain disorder, defined as use of any analgesic medication on more days than not during the four weeks preceding the acute episode of pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Lidocaine; Administered at a dose of 2 mg/kg over 5 minutes	Drug: Lidocaine Iv; 2 mg/kg over 5 minutes; Other Names: Xylocaine
Active Comparator: Intravenous Hydromorphone; Administered at a dose of 1 mg over 5 minutes	Drug: HYDROmorphone Injection; 1 mg over 5 minutes; Other Names: Dilaudid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Improvement in Pain at 90 Minutes	The difference between the pain score at time 0 and 90 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sufficient Pain Relief	Does the patient require off-protocol medication for additional pain relief? Off-protocol defined as any opiate or NSAID	From administration of study drug until patient leaves the emergency department, up until 3 hours from administration of study drug.
Side Effects	Yes or no, did the patient have any side effects, defined as any new symptom after the administration of the study drug.	15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes and at 7 days
Serious Adverse Event	Yes or no, did the patient suffer a serious adverse event? Defined as death, requiring or prolonging inpatient hospitalization, resulting in persistent or significant disability/incapacity, or is considered a significant medical event by the investigator based off of medical judgement.	180 minutes after administration of study drug
Improvement in Numerical Pain Score at 15 Minutes	The difference between the pain score at time 0 and 15 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	15 minutes
Improvement in Numerical Pain Score at 30 Minutes	The difference between the pain score at time 0 and 30 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	30 minutes
Improvement in Numerical Pain Score at 60 Minutes	The difference between the pain score at time 0 and 60 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	60 minutes
Improvement in Numerical Pain Score at 120 Minutes	The difference between the pain score at time 0 and 120 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	120 minutes
Improvement in Numerical Pain Score at 150 Minutes	The difference between the pain score at time 0 and 150 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	150 minutes
Improvement in Numerical Pain Score at 180 Minutes	The difference between the pain score at time 0 and 180 minutes. Pain score ranges from 0 (no pain) to 10 (maximum pain).	180 minutes
Patient Preference for the Medication They Received	If the patient were to come to the ED again for the same complaint, would they want the same study drug they received?	Day 7
Medication for Side Effects	Are any medications required to control medication side effects, defined as any new symptom after the administration of the study drug?	15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and 180 minutes
Administration of Naloxone	Yes or no, was naloxone required after the patient received the study drug?	15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and at 180 minutes
Change in Disposition	Yes or no, did the patients disposition change as a consequence of administration of the study drug? Example would be an adverse outcome resulting in hospitalization or other escalation of care.	15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and at 180 minutes
Missed Diagnosis	Yes or no, did the patient have a new diagnosis within the next week?	7 days after administration of study drug

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute
• Investigators: Principal Investigator: Elliott Chinn, DO, Hennepin County Medical Center, Minneapolis

Publications and helpful links

General Publications

• Vigneault L, Turgeon AF, Cote D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0.
• Kranke P, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, Eberhart LH, Poepping DM, Weibel S. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev. 2015 Jul 16;(7):CD009642. doi: 10.1002/14651858.CD009642.pub2.
• Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol. 2012 May 4;12:13. doi: 10.1186/1471-2490-12-13.
• Firouzian A, Alipour A, Rashidian Dezfouli H, Zamani Kiasari A, Gholipour Baradari A, Emami Zeydi A, Amini Ahidashti H, Montazami M, Hosseininejad SM, Yazdani Kochuei F. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016 Mar;34(3):443-8. doi: 10.1016/j.ajem.2015.11.062. Epub 2015 Dec 1.
• Soleimanpour H, Hassanzadeh K, Mohammadi DA, Vaezi H, Esfanjani RM. Parenteral lidocaine for treatment of intractable renal colic: a case series. J Med Case Rep. 2011 Jun 29;5:256. doi: 10.1186/1752-1947-5-256.
• Sun Y, Li T, Wang N, Yun Y, Gan TJ. Perioperative systemic lidocaine for postoperative analgesia and recovery after abdominal surgery: a meta-analysis of randomized controlled trials. Dis Colon Rectum. 2012 Nov;55(11):1183-94. doi: 10.1097/DCR.0b013e318259bcd8. Erratum In: Dis Colon Rectum. 2013 Feb;52(2):271.
• Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis. Anesth Analg. 2005 Dec;101(6):1738-1749. doi: 10.1213/01.ANE.0000186348.86792.38.
• Ventham NT, Kennedy ED, Brady RR, Paterson HM, Speake D, Foo I, Fearon KC. Efficacy of Intravenous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J Surg. 2015 Sep;39(9):2220-34. doi: 10.1007/s00268-015-3105-6.
• Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg. 2008 Nov;95(11):1331-8. doi: 10.1002/bjs.6375.
• Fitzpatrick BM, Mullins ME. Intravenous lidocaine for the treatment of acute pain in the emergency department. Clin Exp Emerg Med. 2016 Jun 30;3(2):105-108. doi: 10.15441/ceem.15.103. eCollection 2016 Jun.
• Vahidi E, Shakoor D, Aghaie Meybodi M, Saeedi M. Comparison of intravenous lidocaine versus morphine in alleviating pain in patients with critical limb ischaemia. Emerg Med J. 2015 Jul;32(7):516-9. doi: 10.1136/emermed-2014-203944. Epub 2014 Aug 21.
• Clattenburg EJ, Nguyen A, Yoo T, Flores S, Hailozian C, Louie D, Herring AA. Intravenous Lidocaine Provides Similar Analgesia to Intravenous Morphine for Undifferentiated Severe Pain in the Emergency Department: A Pilot, Unblinded Randomized Controlled Trial. Pain Med. 2019 Apr 1;20(4):834-839. doi: 10.1093/pm/pny031.
• Chinn E, Friedman BW, Naeem F, Irizarry E, Afrifa F, Zias E, Jones MP, Pearlman S, Chertoff A, Wollowitz A, Gallagher EJ. Randomized Trial of Intravenous Lidocaine Versus Hydromorphone for Acute Abdominal Pain in the Emergency Department. Ann Emerg Med. 2019 Aug;74(2):233-240. doi: 10.1016/j.annemergmed.2019.01.021. Epub 2019 Feb 26.

Helpful Links

• Emergency Department Visits for Chest Pain and Abdominal Pain: United States, 1999-2008

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: lidocaine; hydromorphone; abdominal pain
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Signs and Symptoms, Digestive; Renal Colic; Emergencies; Abdominal Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine; Hydromorphone
• Other Study ID Numbers: 20202020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No