The Effect of Intravenous Erythromycin on Gastric Emptying in Non-fasted Patients Before Emergency Total Anesthesia - Full Text View

Sponsor:	University Hospital, Geneva
Information provided by (Responsible Party):	Christoph Czarnetzki, University Hospital, Geneva
ClinicalTrials.gov Identifier:	NCT00827216

Purpose

In this study the investigators want to investigate the effect of a short intravenous infusion of Erythromycine on gastric emptying on patients considered "full stomac" and scheduled for Emergency operation. A gastroscopy will be done after intubation to controll the effect of the perfusion.

Condition	Intervention	Phase
Aspiration of Gastric Contents Gastric Emptying	Drug: Placebo Drug: Erythromycin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Effect of Intravenous Erythromycin on Gastric Emptying in Patients Undergoing Rapid Sequence Intubation for Full Stomach - A Randomised, Placebo-controlled, Double-blind Study

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Erythromycin Gluceptate Erythromycin Erythromycin stearate Erythromycin ethylsuccinate Erythromycin estolate

U.S. FDA Resources

Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:

Immediately after intubation an upper GI endoscopy will be done. The following primary endpoint will be recorded: Stomach clear from any content: yes or no (dichotomous). [ Time Frame: 10 minutes ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Acidity and Estimation of the volume of gastric content if stomach not empty (ml). [ Time Frame: 10 minutes ] [ Designated as safety issue: No ]
Drug-related allergic reactions. [ Time Frame: 30 minutes ] [ Designated as safety issue: Yes ]
Arrhythmia. [ Time Frame: 30 minutes ] [ Designated as safety issue: Yes ]
Gastrointestinal cramps after study drug administration but before intubation. [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
Nausea or vomiting after study drug administration but before intubation. [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
Regurgitation with or without broncho-aspiration at induction. [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2009
Estimated Study Completion Date:	February 2012
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Physiologic saline	Drug: Placebo For all patients, a standardised volume of 10 ml of the study drug (will be diluted in 90 ml NaCl 0.9% (total volume, 100 ml). Both, the study drug and the 90 ml NaCl bag will be prepared by the pharmacy. Using sterile syringes, the investigator will withdraw from this solution as many millilitres as necessary to obtain a volume that corresponds to 1 ml per kg bodyweight of the patient (i.e. for a 67 kg patient, 33 ml would be with withdrawn). Thus, the maximum volume that can be administered to a patient will be 100 ml (i.e. for a patient weighing ≥100 kg). Twenty minutes prior to the scheduled induction of anaesthesia, patients will receive their study drug solution as an intravenous infusion during 5 min.
Active Comparator: Erythromycine	Drug: Erythromycin For all patients, a standardised volume of 10 ml of the study drug (will be diluted in 90 ml NaCl 0.9% (total volume, 100 ml). Both, the study drug and the 90 ml NaCl bag will be prepared by the pharmacy. Using sterile syringes, the investigator will withdraw from this solution as many millilitres as necessary to obtain a volume that corresponds to 1 ml per kg bodyweight of the patient (i.e. for a 67 kg patient, 33 ml would be with withdrawn). Thus, the maximum volume that can be administered to a patient will be 100 ml (i.e. for a patient weighing ≥100 kg). Twenty minutes prior to the scheduled induction of anaesthesia, patients will receive their study drug solution as an intravenous infusion during 5 min. The regimen corresponds to 3 mg/kg of erythromycin. Other Name: Erythrocine®

Arms

Assigned Interventions

Placebo Comparator: Physiologic saline

Drug: Placebo

For all patients, a standardised volume of 10 ml of the study drug (will be diluted in 90 ml NaCl 0.9% (total volume, 100 ml). Both, the study drug and the 90 ml NaCl bag will be prepared by the pharmacy. Using sterile syringes, the investigator will withdraw from this solution as many millilitres as necessary to obtain a volume that corresponds to 1 ml per kg bodyweight of the patient (i.e. for a 67 kg patient, 33 ml would be with withdrawn). Thus, the maximum volume that can be administered to a patient will be 100 ml (i.e. for a patient weighing ≥100 kg). Twenty minutes prior to the scheduled induction of anaesthesia, patients will receive their study drug solution as an intravenous infusion during 5 min.

Active Comparator: Erythromycine

Drug: Erythromycin

For all patients, a standardised volume of 10 ml of the study drug (will be diluted in 90 ml NaCl 0.9% (total volume, 100 ml). Both, the study drug and the 90 ml NaCl bag will be prepared by the pharmacy. Using sterile syringes, the investigator will withdraw from this solution as many millilitres as necessary to obtain a volume that corresponds to 1 ml per kg bodyweight of the patient (i.e. for a 67 kg patient, 33 ml would be with withdrawn). Thus, the maximum volume that can be administered to a patient will be 100 ml (i.e. for a patient weighing ≥100 kg). Twenty minutes prior to the scheduled induction of anaesthesia, patients will receive their study drug solution as an intravenous infusion during 5 min. The regimen corresponds to 3 mg/kg of erythromycin.

Other Name: Erythrocine®

Detailed Description:

Urgent or emergency surgery requires that fasting rules observed in elective settings are not respected. Patients who are anesthetized in such conditions are at risk for regurgitation and subsequent broncho-aspiration during induction of anaesthesia due to a full stomach; they often have ingested food or liquids before the injury, or they may have swallowed blood from oral or nasal injuries. Also, gastric emptying is delayed in these patients due to the stress of trauma.1 Already in 1946, Mendelson described the consequences of bronchoaspiration.2 Since, anaesthetists and emergency physicians have tried to avoid broncho-aspiration in emergency patients using premedication with pro-kinetic drugs (for instance, metoclopramide) or its complications with antacid substances, and through the use of a rapid sequence intubation procedure with cricoid pressure.

The incidence of aspiration is low, about 1.4 to 6 in 10'000 anaesthetics.3 About 6 in 100'000 anaesthetics will lead to a pulmonary complication due to broncho-aspiration and about 1 in 100'000 patients is likely to die due to aspiration.4 Thus, although episodes of broncho-aspiration are rare, efficacious prevention of this potentially lethal complication is important. One method to reduce the risk of broncho-aspiration during induction of anaesthesia is the pharmacological reduction of the gastric content (i.e. pre-treatment).

The primary objective of this study is to investigate the effect of a short intravenous infusion of erythromycin 3 mg/kg, administered 20 min before intubation on gastric emptying, in adults scheduled for rapid sequence intubation for full stomach. After intubation a gastroscopy will be done to see if there is any content in the stomac. The secondary objective is the assessment of tolerability and safety of a single intravenous dose of preoperative erythromycin in surgical patients.

This study is a single centre, stratified (according to emergency setting), randomised, placebo-controlled, double-blinded study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adults, age ≥18 years, male or female.
American Society of Anaesthesiology [ASA] status I, II or III.
Non-starving patients presenting for surgery.
Patients able to read and understand the information sheet and to sign the consent form.
If the patient is female and of childbearing potential, she must have a negative pregnancy test

Exclusion Criteria:

A history of allergy or hypersensitivity to erythromycin or other macrolides.
Concomitant use of terfenadine, astemizole, cisapride, pimozid, cyclosporine, clarithromycine.
Patient with acute intermittent porphyria.
Acute or subacute necrosis of the liver, acute or subacute hepatitis, acute liver trauma
Acute renal failure, acute glomerulonephritis, nephritic syndrome, chronic renal failure with electrolyte disorders, uremia
Exacerbated asthma, exacerbated chronic obstructive lung disease, acute pulmonary infection
Coronary heart disease (unstable angina, MI within the last 6 months), decompensated cardiac insufficiency, aortic aneurysm
Polyneuropathy (for instance, due to diabetes mellitus)
Patients with oesophageal and pharyngeal disease (i.e. oesophageal varices, oesophageal and pharyngeal cancer, Zenker's diverticulum).
Status after gastric surgery, gastric bypass surgery, Nissen operation
Patients with life threatening illness or injury needing immediate surgery
Patients with moderate to severe head trauma (GCS on admission <13)
Psychological or psychiatric disorders.
Dementia or inability to understand the study protocol.
Women who are pregnant or are breast feeding.
Patient scheduled for ileus surgery.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827216

Contacts

Contact: Christoph A Czarnetzki, MD, MBA	0041223733311	christoph.czarnetzki@hcuge.ch
Contact: Martin R Tramer, MD, PhD	0041223723311	martin.tramer@hcuge.ch

Locations

Switzerland
University Hospital of Geneva	Recruiting
Geneva, Switzerland, 1211
Contact: Christoph A Czarnetzki, MD, MBA 0041223723311 ext 7958558 christoph.czarnetzki@hcuge.ch
Contact: Martin R Tramèr, MD, Dphil 0041223723311 ext 7958621 martin.tramer@hcuge.ch
Sub-Investigator: Jean Luc Waeber, MD
Sub-Investigator: Christopher Lysakowski, MD
Sub-Investigator: Georges Savoldelli, MD
Sub-Investigator: Emiliano Giostra, MD
Sub-Investigator: Jean Louis Frossard, MD
Sub-Investigator: Laurent Spahr, MD

Sponsors and Collaborators

University Hospital, Geneva

Investigators

Principal Investigator:	Christoph A Czarnetzki, MD, MBA	Division of Anesthesiology, University Hospital of Geneva
Study Chair:	Martin R Tramer, MD, PhD	Division of Anesthesiology, University Hospital of Geneva

More Information

Publications:

Frossard JL, Spahr L, Queneau PE, Giostra E, Burckhardt B, Ory G, De Saussure P, Armenian B, De Peyer R, Hadengue A. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Gastroenterology. 2002 Jul;123(1):17-23. Erratum in: Gastroenterology 2002 Dec;123(6):2162.

Boivin MA, Carey MC, Levy H. Erythromycin accelerates gastric emptying in a dose-response manner in healthy subjects. Pharmacotherapy. 2003 Jan;23(1):5-8.

Bouvet L, Duflo F, Bleyzac N, Mion F, Boselli E, Allaouchiche B, Chassard D. Erythromycin promotes gastric emptying during acute pain in volunteers. Anesth Analg. 2006 Jun;102(6):1803-8.

Kopp VJ, Mayer DC, Shaheen NJ. Intravenous erythromycin promotes gastric emptying prior to emergency anesthesia. Anesthesiology. 1997 Sep;87(3):703-5. No abstract available.

Responsible Party:	Christoph Czarnetzki, Responsable Investigator, University Hospital, Geneva
ClinicalTrials.gov Identifier:	NCT00827216 History of Changes
Other Study ID Numbers:	NAC 06-225, Swissmedic 2008 DR 2321
Study First Received:	January 21, 2009
Last Updated:	November 8, 2011
Health Authority:	Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:

Gastric emptying
emergency anesthesia
gastric emptying
intravenous erythromycin

Additional relevant MeSH terms:

Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Anesthetics
Erythromycin stearate
Erythromycin
Erythromycin Estolate
Erythromycin Ethylsuccinate
Central Nervous System Depressants

Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 09, 2012