Sedation Methods During Cataract Surgery

NCT ID: NCT03054103

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-03
• Study Completion Date: 2016-11-11

Brief Summary

Background: Phacoemulsification is the most common surgical procedure performed in the United States and European Union and sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. The investigators have administered ketamine in addition to midazolam in this regard. To study the effectiveness of this technique, The investigators proposed a study to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and intravenous (IV) conscious sedation.

Methods: In a free-standing Outpatient Surgery Center, the investigators conducted a randomized, double-masked, 3-arm, prospective comparison of IV midazolam only vs. midazolam with ketamine 5 mg IV vs. midazolam with ketamine 10 mg IV. The investigators then measured a single surgeon's assessment of surgical conditions, self-reported patient satisfaction, postoperative pain score, and duration of postoperative stay. The investigators also analyzed the dose of midazolam required to meet subjective anxiolysis in each group.

Detailed Description

Phacoemulsification is the most common surgical procedure performed in the United States and European Union. In addition, the number of diagnoses of cataracts is expected to double from 25,000,000 in 2010 to 50,000,000 in 2050 while the incidence of phacoemulsification is also increasing. Therefore, any attempt to optimize outcome and efficiency is significant.

Sedation is commonly used during phacoemulsification to help alleviate patient anxiety and prevent the patient from interfering with the procedure. However, a great deal of variation exists in anesthetic management of these cases. Investigators have published use of a number of agents for sedation in the literature. These include midazolam, clonidine, propofol, fentanyl, dexmedetomidine, remifentanil, and oral diazepam. Intravenous (IV) clonidine has a half-life of 9-13 h and increased risk of postoperative hypotension. Propofol causes disinhibition and it has to be titrated during surgery to prevent oversedation. Opioids carry an increased risk of respiratory depression, prolonged sedation, as well as delirium in the elderly. Finally, oral medications do not allow for quick dose adjustments during surgery.

Intravenous midazolam is commonly used for sedation during phacoemulsification and other minor procedures. It has properties as an anxiolytic, muscle relaxant, and it is effective at reducing intraocular pressure. However, anxious patients administered benzodiazepines may require higher doses during cataract surgery which can lead to oversedation or disinhibition with subsequent patient movement. These responses can reduce the patient's ability to follow simple commands which can affect surgical outcome. Additionally, patients who receive too much sedation may fall asleep and wake up startled, similarly compromising the outcome of the surgery.

In the search for additional medications that can improve surgical conditions and patient comfort during phacoemulsification, the investigators explored the use of a medication that can improve analgesia and reduce patient movement during procedures, namely ketamine. Ketamine is an NMDA antagonist with both sedative and analgesic properties and has minimal effects on respiration. Ketamine has been used to premedicate and sedate patients undergoing day care procedures without adverse effects, and patients, typically, remain cooperative albeit being sedated. These properties along with its relatively short elimination half-life of 2 h (compared with 3-4 h for midazolam) make ketamine an attractive agent for sedation during monitored anesthesia care (MAC) for cataract surgery.

The purpose of this study was to determine if adding low-dose ketamine to midazolam has any beneficial (or negative) effects on operating conditions, patient satisfaction, and recovery during and after unilateral phacoemulsification procedures performed using topical anesthesia and IV conscious sedation.

The investigators measured the surgeon's assessment of the participant's cooperation during surgery according to a predetermined Likert scale. The investigators also recorded the following outcome measures regarding each participant's surgery: 1) total dose of midazolam, 2) average time spent in the procedural room, 3) postoperative length of stay (LOS), and 4) average postoperative pain score. The subjects received a survey inquiring about the subjects' comfort and sedation level during surgery. Finally, the investigators recorded the following demographic data for all participants: gender, age, psychiatric diagnoses, and use of CNS, psychiatric, or opioid medications.

Statistical Analysis The investigators used Fisher's exact test for examining data expressed as percentages, and Students t-test for yes/no data, and repeated measures ANOVA for 3 group analysis (LOS, surgical duration). The investigators judged significance at a P-value of 0.05. The investigators utilized a generalized estimated equations (GEE) to fit a logistic model to assess differences in the responses of patients based on amount of ketamine received. The GEE approach can fit models to correlated outcomes, as in the case where subjects had more than one procedure performed.

Conditions

Phacoemulsification; Cataract

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Midazolam alone

Drug: Midazolam titrated 0.5-2.0 mg + normal saline placebo. Midazolam + Normal saline

Group Type: PLACEBO_COMPARATOR

Midazolam + Normal saline

Intervention Type: DRUG

Preoperative control: Normal saline placebo given preoperatively. Then protocol followed for titration of midazolam up to 2 mg IV at beginning and during case.

Midazolam + Ketamine 5 mg

Drug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 0.5 ML. Midazolam + Ketamine 10 MG/ML: 0.5 ML

Group Type: ACTIVE_COMPARATOR

Midazolam + Ketamine 10 MG/ML: 0.5 ML

Intervention Type: DRUG

5 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.

Midazolam + Ketamine 10 mg

Drug: Midazolam titrated 0.5-2.0 mg + Ketamine 10 MG/ML: 1 ML. Midazolam + Ketamine 10 MG/ML: 1 ML

Group Type: ACTIVE_COMPARATOR

Midazolam + Ketamine 10 MG/ML: 1 ML

Intervention Type: DRUG

10 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.

Interventions

Midazolam + Ketamine 10 MG/ML: 0.5 ML

5 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.

Intervention Type: DRUG

Midazolam + Ketamine 10 MG/ML: 1 ML

10 mg ketamine IV given just prior to onset of case. Then titrated midazolam up to 2 mg IV at beginning and during case.

Intervention Type: DRUG

Midazolam + Normal saline

Preoperative control: Normal saline placebo given preoperatively. Then protocol followed for titration of midazolam up to 2 mg IV at beginning and during case.

Intervention Type: DRUG

Other Intervention Names

Ketalar; Ketalar; NS

Eligibility Criteria

Exclusion Criteria

• Patients younger than 18, older than 80, those with a serum creatinine >3 mg/dl, advanced liver disease (liver enzymes twice the normal range or higher), and those with an allergy to any of the study medications were excluded from the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy N Harwood, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Other Identifiers

IRB00031444

Identifier Type: -

Identifier Source: org_study_id