Ketamine (Ketalar)

Anesthesia Implications

Classification: NMDA antagonist, phencyclidine derivative
Therapeutic Effects: Analgesia, Amnesia, Bronchodilator, Positive Inotrope (indirect), Negative Inotrope (direct)
Time to Onset: IV: 1-2 minutes; IM: 5-10 minutes; PO: 20-30 minutes

Duration: IV: 20-60 minutes; IM: 30-120 minutes; PO: 60-90 minutes

Contraindications

Pre-eclampsia: Causes sympathetic stimulation which will exacerbate hypertension.
Hx of schizophrenia or active psychosis: Ketamine can worsen the symptoms of these disorders.
History of seizures: Ketamine can induce seizures.
Hyperthyroidism: exaggerates an already overactive SNS.
Adrenal suppression (addison’s disease, hypothyroidism, etc): ketamine will have direct negative inotropic affects.
Patients with increased intracranial or intraocular pressures: ketamine increases these pressures.
Surgeries requiring an immobile eye: ketamine causes nystagmus.
Vascular surgeries: not an absolute contraindication, but ketamine can increase blood pressure.
Head Trauma: May increase intracranial pressures
Pulmonary Hypertension: VERY debatable. Many would agree that the affects on pulmonary hypertension are minimal and the pros of using ketamine outweigh the cons.

Primary Considerations

Ketamine increases sympathetic nervous system responses (sympathomimetic).  Does not depress ventilation.  Increases blood pressure, heart rate, laryngeal reflexes (reduces the chances of aspiration), secretions, cerebral blood flow, cerebral metabolism (CMRO2), intraoccular pressure (highly debated), nausea, and postoperative vomiting (PONV).   PONV is rare when PO ketamine is used as premedication.  Nystagmus and hallucinations are also potential side effects.

Enhances MEPs/SSEPs

Ketamine will have a direct negative inotropic affect on the heart.  This is overridden by the indirect positive inotropic affects in patients with healthy adrenal function.  In patients that have adrenal suppression/depletion anticipate negative inotropic affects.

Propofol and/or Midazolam should be co-administered with ketamine to reduce postoperative hallucinations/delirium.  Hallucinations and nightmares are uncommon when the dose does not exceed 1 mg/kg. Quiet awakening in a dark environment has also shown to reduce postoperative hallucinations.  The side effect of hallucinations are the primary reason ketamine is a second-tier induction agent (used when the typical agents are contraindicated).

An antisialogugue such as glycopyrrolate should be given to counteract the copious secretions that can be seen as a side-effect of ketamine

Ketamine MAY produce amnesia. The results are variable, so this affect should not be relied upon.

Enhances evoked potential monitoring.

Ketamine is associated with PONV, but to a lesser degree than opioids, so practices sometimes include using ketamine as an analgesic instead of opioids in patients that are particularly at risk for PONV.

Ketamine may induce seizures in patients with high blood levels of Theophylline.

Ketamine effectively counteracts many of the cardiorespiratory affects of propofol.  For this reason, many practitioners will mix the two, creating what has been dubbed as “ketofol”.  However, ketamine has a longer half-life, and will outlast propofol.  This is particularly notable in long cases and may result in a delayed emergence.

Ketamine will have additive and synergistic affects with other sedatives, potentially creating deep sedation and/or general anesthesia

Ketamine produces a dissociative state characterized by open eyes and a nystagmic gaze.

Ketamine has excellent analgesia properties.  This can be beneficial in patients where opioid administration is limited.

Paradoxical cortical excitation produced by ketamine can disrupt EEG monitoring, falsely producing what appears to be light anesthesia.  Slow infusions can reduce the occurrence of this phenomenon.

Neuraxial blocks using ketamine should use preservative-free S-ketamine.  The neurotoxic risks have not been established for R-ketamine so it should not be used for neuroaxial anesthesia

IM Ketamine is very effective as an agent for patients that are problematic/combative.  The literature points repeatedly to handicapped and pediatric patients of this category.

In spite of the possibilities of sympathetic responses, ketamine has been used without difficulties in patients with Parkinson’s disease.

Safe to use in patients with porphyria and pemphigus vulgaris (PV)

Controversial, but ketamine has been used to prolong the blockade of caudal blocks.

Proposed as the induction agent of choice in hypothyroid patients.

Sympathetic stimulation and bronchodilation makes this drug a choice agent for patients with hypovolemia and reactive airways respectively.

Because ketamine supports the cardiac index better than the other induction agents, ketamine is also the induction agent of choice for patients with pericardial effusion and pericardial tamponade.

Can be used in pediatric patients as pharmacologic preparation for surgery.  The PO dose is 5 – 10 mg/kg, and should be given 20-30 minutes prior to induction.  The duration will last 60 – 90 minutes

IV push dose

Analgesia:
0.25-1.0 mg/kg; Most typical clinically is 10-20 mg doses, repeated Q 2-5 minutes, not to exceed 1mg/kg during a 30 minute period.

IV induction dose: 1-2.5 mg/kg

Combining ketamine with Dexmedetomidine is becoming a favored practice as ketamine will reduce the respiratory depressing affects of Dexmedetomidine (which are minimal), while Dexmedetomidine will reduce the psychomimetic effects of ketamine.  This combination is as follows: Loading dose of Dexmedetomidine (1 ug/kg over 10 minutes) followed by a Ketamine Infusion: 0.2 – 0.7 ug/kg/hour.

OB: in low doses (0.2 – 0.4 mg/kg), ketamine provides analgesia to the parturient without neonatal depression. Doses > 2 mg/kg will cause uterine hypertonus and reduced uterine blood flow (UBF) in the parturient.

Very little cardiovascular/respiratory depression when administered in low doses (0.25 – 0.50 mg/kg)

Neonate:  used as an induction agent in neonates with cardiovascular instability (IV: 2 mg/kg, IM: 4-5 mg/kg)

IV infusion dose

Analgesia: 0.25 – 0.5 mg bolus followed by 2 – 4 ug/kg/min. This formula is great for analgesia and is opioid sparing

Phantom limb pain: Ketamine is a very effective treatment for phantom limb pain, which is experienced in approximately 80% of amputees. In the cited article, an infusion of 300 mcg/kg + 2mg of versed in 60ml of crystalloid, given over 3 hours, and every other day for 12 days, substantially reduced/eliminated these problems.

IM dose

Sedation: 2-4 mg/kg; Intubation: 3-5 mg/kg

Method of Action

NMDA receptor blockade

Metabolism

Hepatic (CYP450 3A4). Metabolized to norketamine which has 1/3 the affects of the parent drug

Additional Notes
PO dose for Adults and PEDs= 5-10 mg/kg (cannot be used for emergent intubation)