Ketamine for Control of the Agitated Patient

Can Ketamine be used for the control of the agitated patient?

CASE

A patient is brought into the emergency department in an agitated state. There is a history of recent drug use, potentially amphetamines. The patient has been treated with Midazolam and doses of Droperidol are added. However there is a significant delay in the effect of these medications and the patient is increasingly combative and presents a danger to themselves and to the emergency staff. Given the patient’s state and the need for a CT brain, the patient is intubated.

Is there a better way? I think there is. read on.

A study by Lin et al, looked at the use of Ketamine to control agitation in the emergency department. They compared Ketamine to haloperidol plus lorazepam

STUDY DESIGN: What they did

Randomised, prospective, single institution, open label pilot study.

Patients were eligible if at least 18 years of age  and had a diagnosis of combative agitation.

Patients were randomised to either of:

1. Ketamine 4mg/kg IM, or 1mg/kg IV (MAX 500mg) (n = 41)
2. Haloperidol 10mg IM/IV plus Lorazepam 2mg IM/IV (n=43)
   1. 61% of patients had the total dose
   2. 20% received Haloperidol 5mg and Lorazepam 2mg

93% received IM doses

PRIMARY OUTCOME

Sedation at 5 minutes (RASS(Richmond Agitation Sedation Scale) Score less than or equal to 0)

RASS score of 0 means a patient is alert and calm. Levels of -1 to -5 indicated increasing levels of sedation.

Results

• 22% of ketamine group achieved the primary outcome at 5 minutes compared to 0% in haloperidol plus lorazepam group
• Median time to sedation was 15 minutes in Ketamine group and 36.5 minutes in Haloperidol plus lorazepam group.

SECONDARY OUTCOMES

1. Adequate sedation at 15 minutes
2. Time to sedation
3. Median RASS score at 30 minutes
4. If other sedation medications needed to be administered

Results

• RASS score at 30 minutes was -1 in ketamine group and 0 in Haloperidol and Lorazepam group. This indicates a better level of sedation.

ADVERSE EVENTS

These were documented:

1. Tachycardia
2. Hypertension
3. Hypoxia
4. QTc>450ms
5. Arrhythmia
6. Cardiac Arrest
7. Respiratory depression requiring intubation
8. Patient reported nausea

Results

• Hypertension and Tachycardia
  • Both were significantly more common in the Ketamine group.
    • An increased blood pressure was defined as  an increase of >20mmHg in either systolic or diastolic blood pressure. The median BP was actually 132/88 in the Ketamine group vs 134/79 in the Haloperidol Lorazepam group…So not a great deal of difference.
    • Tachycardia was defined as a rise of > 10bpm. The median heart rate was 110 in the Ketamine vs 100 in the Haloperidol plus  Lorazepam group.
• One case of bradycardia, hypoxia and cardiac arrest occurred in the Haloperidol plus Lorazepam group.
• No significant difference between the two groups in terms of :
  • QTc>450ms
  • Hypoxia
    • Hypoxia(SpO2 <92%) was higher in the Ketamine group (21% vs 10%), but did not reach statistical significance. It improved in most cases, with supplemental oxygen.
      • It resulted in one intubation in the Ketamine group.
  • Hypotension
  • Nausea
  • Hypersalivation

LIMITATIONS

There is a potential for selection bias in this study, as not all patients presenting were admitted. Also the doses of Haloperidol plus Lorazepam were altered to account for patient co-morbidities. Perhaps increased doses of Haloperidol and Lorazepam could have been used. However unlike Ketamine, which has no further dose response, once dissociation is reached, administration of increased doses of other sedative drugs can result in a dose response continuum, with potential hypotension and loss of airway reflexes.

PUTTING IT ALL TOGETHER

Ketamine had a more rapid onset of sedation and results in a deeper level of sedation, than Haloperidol plus Lorazepam. There is a potential increase in heart rate and blood pressure with ketamine and a non-significant increase in hypoxia.

A larger study needs to be done, but it appears that we can use Ketamine to control the agitated patient in the emergency department, especially those with combative agitation.

Reference

Lin J et al. Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomised study. Am J of Emerg Med 2020 Apr 11;S0735-6757(20)30241-2. doi: 10.1016/j.ajem.2020.04.013.Online ahead of print.