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Ketamine: Comparison of IV Push vs. IV Drip

Comparison of Intravenous Push Dose of Low Dose Ketamine to Short Infusion of Low Dose Ketamine for Treatment of Moderate to Severe Pain in the Emergency Department: A Prospective, Randomized, Double-Blind Study

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02363270
Enrollment
48
Registered
2015-02-13
Start date
2015-04-01
Completion date
2017-02-28
Last updated
2017-11-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain

Keywords

Analgesia, ketamine

Brief summary

Our previous published research comparing the efficacy of intravenous ketamine to morphine has shown ketamine to provide equivalent relief of moderate to severe acute pain in emergency medicine patients. Secondary analysis of the previous published research has also revealed ketamine to have statistically more side effects. The investigators believe that increasing the time of administration of the ketamine, from a push injection to a drip infusion, will minimize the side effects experienced by recipients of ketamine.

Detailed description

Ketamine is a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist that blocks the release of excitatory neurotransmitter glutamate and provides anesthesia, amnesia and analgesia by virtue of decreasing central sensitization and wind-up phenomenon. At low (sub-dissociative, analgesics) doses of 0.1-0.4 mg/kg either as an adjunct to opioid analgesics or as a single agent, ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability. In addition, the low-dose of ketamine increases the analgesic potency of opioids thus decreasing their requirements. Several recent studies of low-dose ketamine administered together with morphine provided acceptable pain relief to 55-60% of patients with minor side effects of dizziness, nausea and feeling of unreality. More recently the investigators conducted a research comparing Low-Dose Ketamine to Morphine for Moderate to Severe Pain in the Emergency Department with respect its analgesic efficacy and safety. Results demonstrated similar pain relief at 30 min between 2 groups. However, 70% of patients in ketamine group had minor side effects at 5 min and 35% of patients at 30 min, as compared to 51% at 5 min. and 31% at 15 min. in the morphine group. The most common side effects reported by ketamine patients were dizziness, nausea, feeling of unreality, and mood changes. Based on the above mentioned data from our previous published research study, we hypothesized that low-dose ketamine given as a short infusion over 15 min will provide similar analgesic efficacy as an intravenous push-dose but with much less side effects. There are several research papers that support our hypothesis. A prospective, randomized trial compared two analgesic regimens, morphine with ketamine (K group) or morphine with placebo (P group) for severe acute pain in 73 trauma patients with a visual analog scale (VAS) score of at least 60/100. Morphine was administered at 0.1mg/kg and patients in the K group received 0.2 mg/kg of intravenous ketamine over 10 minutes, and the patients in the P group received isotonic sodium chloride solution. The results showed comparable change in VAS score at 30 minutes (34 mm (K) vs. 39 mm (P)) but reduced morphine consumption in the ketamine group (0.14 mg/kg (K) vs 0.2 mg/kg (P)). A double-blind trial of 40 adult patients with acute musculoskeletal trauma compared a low-dose ketamine by subcutaneous infusion (0.1 mg/kg/h) with intermittent morphine (0.1 mg/kg IV every 4 hours ) and demonstrated better pain relief, less sedation and less nausea and vomiting with ketamine infusion than with intermittent morphine. In addition, none of the patients in ketamine group required supplementary analgesia. A prospective case series of 20 unselected adult ED patients with acute pain that evaluated analgesic feasibility of low-dose ketamine infusion was conducted in an urban public hospital over a course of 5 months. Patients received 15mg of intravenous push dose ketamine that was followed by continuous ketamine infusion at 20mg per hour for one hour. Optional morphine (4 mg) was offered at 20, 40 and 60 minutes. Pain intensity was assessed at regular intervals for 2 hours using a 10-point verbal numerical rating scale (NRS), along with vital signs and levels of sedation. Results showed that fifteen patients reported clinically significant pain relief at 60 minutes and 13 at 120 minutes; and eighteen patients reported mild or modest side effects including dizziness, fatigue and headache.

Interventions

PROCEDUREKetamine

IV Push or or IV Drip

Sponsors

Antonios Likourezos
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

* Emergency Medicine patients * Adult patients (18-65 years of age) * Moderate to severe pain (Numeric Pain Rating Score =5). * Patients must be awake, alert and oriented to time, place and person. * Patients must be able to demonstrate understanding of the informed consent, and also able to verbalize how much pain they are having on the 10 point Numeric Rating Pain Scale, and the nature of the side effects they may be experiencing from the IV analgesia

Exclusion criteria

* Patients with cognitive deficits that are not able to demonstrate understanding as described above. * Patient's reported weight of less than 45kg or more than 115kg. * Patients with altered mental status, alcohol intoxication, eye trauma. * Patients with hemodynamic instability (Systolic Blood pressure \<90), and malignant hypertension. * allergy to ketamine * Pregnancy or breast feeding.

Design outcomes

Primary

MeasureTime frameDescription
Overall Rate of Feeling Unreality30 minutesOverall rate of feeling of unreality as measured by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA)

Countries

United States

Participant flow

Participants by arm

ArmCount
IV Push Group
Ketamine medication given via IV Push. IV Push is the intervention. Ketamine: IV Push or or IV Drip
24
IV Drip Group
Ketamine medication given via IV Drip. IV Drip is the intervention. Ketamine: IV Push or or IV Drip
24
Total48

Baseline characteristics

CharacteristicIV Drip GroupIV Push GroupTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
24 Participants24 Participants48 Participants
Age, Continuous43.56 years
STANDARD_DEVIATION 12.32
45.25 years
STANDARD_DEVIATION 15.12
44.40 years
STANDARD_DEVIATION 13.67
Region of Enrollment
United States
24 participants24 participants48 participants
Sex: Female, Male
Female
12 Participants15 Participants27 Participants
Sex: Female, Male
Male
12 Participants9 Participants21 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 240 / 24
other
Total, other adverse events
22 / 2413 / 24
serious
Total, serious adverse events
0 / 240 / 24

Outcome results

Primary

Overall Rate of Feeling Unreality

Overall rate of feeling of unreality as measured by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA)

Time frame: 30 minutes

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
IV Push GroupOverall Rate of Feeling Unreality22 Participants
IV Drip GroupOverall Rate of Feeling Unreality13 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026