6.

General Anaesthesia – Propofol, Ketamine

Propofol

Propofol is a short-acting medication that results in a decreased level of consciousness and lack of

memory for events. Its uses include the starting and maintenance of general anesthesia, sedation
for mechanically ventilated adults, and procedural sedation. It is also used for status epilepticus if other
medications have not worked. It is given intravenously. Maximum effect takes about two minutes to
occur and it typically lasts five to ten minutes.

Propofol was discovered in 1977. It is on the WHO Model List of Essential Medicines. It has been
referred to as milk of amnesia because of the milk-like appearance of the intravenous
preparation. Propofol is also used in veterinary medicine.

Anesthesia

Propofol is used for induction and maintenance (in some cases) of anesthesia, having largely
replaced sodium thiopental. It can also be administered as part of an anaesthesia maintenance
technique called total intravenous anesthesia using either manually-programmed infusion pumps or
computer-controlled infusion pumps in a process called target controlled infusion or TCI. Propofol is also
used to sedate individuals who are receiving mechanical ventilation but are not undergoing surgery,
such as patients in the intensive care unit. In critically ill patients, propofol has been found to be
superior to lorazepam both in effectiveness and overall cost

Propofol is often used instead of sodium thiopental for starting anesthesia because recovery from
propofol is more rapid and "clear."

Procedural sedation

Propofol is also used for procedural sedation. Its use in these settings results in a faster recovery
compared to midazolam. It can also be combined with opioids or benzodiazepines. Because of its fast
induction and recovery time, propofol is also widely used for sedation of infants and children
undergoing MRI It is also often used in combination with ketamine as the two together have lower rates
of side effects.

Side effects

One of propofol's most frequent side effects is pain on injection, especially in smaller veins. This pain can
be mitigated by pretreatment with lidocaine. Less pain is experienced when infused at a slower rate in a
large vein (antecubital fossa). Patients show great variability in their response to propofol, at times
showing profound sedation with small doses.

Additional side effects include low blood pressure related to vasodilation, transient apnea following

induction doses, and cerebrovascular effects. Propofol has more pronounced hemodynamic effects
relative to many intravenous anesthetic agents.  Propofol can also cause decreased systemic vascular
resistance, myocardial blood flow, and oxygen consumption, possibly through direct vasodilation. There
are also reports that it may cause green discolouration of the urine.
 Possibly as the result of depression of the central inspiratory drive, propofol may produce significant
decreases in respiratory rate, minute volume, tidal volume, mean inspiratory flow rate, and functional
residual capacity.

Diminishing cerebral blood flow, cerebral metabolic oxygen consumption, and intracranial pressure are
also characteristics of propofol administration.  propofol may decrease intraocular pressure by as much
as 50% in patients with normal intraocular pressure.

A more serious but rare side effect is dystonia.

Propofol is also reported to induce priapism in some individuals, and has been observed to suppress
REM sleep stage and to worsen the poor sleep quality in some patients.

Propofol infusion syndrome

Another recently described rare, but serious, side effect. This potentially lethal metabolic derangement
has been reported in critically ill patients after a prolonged infusion of high-dose substance in
combination with catecholamines and/or corticosteroids.

Interactions

The respiratory effects of propofol are increased if given with other respiratory depressants,
including benzodiazepines.

Usual Adult Dose for Anesthesia:

Less than 55 years: Anesthetic Induction: 40 mg IV every 10 seconds until induction onset. Total dose
required is 2 to 2.5 mg/kg with a maximum of 250 mg.

Less than 55 years: Maintenance of Anesthesia: IV infusion: 100 to 200 mcg/kg/min. Maximum dose
20,000 mcg/min. Maximum dose 10,000 mcg/min.
Intermittent bolus: 20 to 50 mg as needed.

Usual Geriatric Dose for Anesthesia:

Elderly, debilitated, or ASA III/IV patients.

Induction: 20 mg every 10 seconds until induction onset (1-1.5 mg/kg). Maximum dose 200 mg
Maintenance: 50-100 mcg/kg/min.
MAC sedation: The maintenance dose is usually 80% of the usual adult dose.

Usual Pediatric Dose for Anesthesia:

3 years to 16 years: Induction: 2.5 to 3.5 mg/kg over 20 to 30 seconds.

Maintenance: 125 to 300 mcg/kg/min.
Ketamine

Ketamine is a medication mainly used for starting and maintaining anesthesia. It induces a trance-like

state while providing pain relief, sedation, and memory loss. Other uses include for chronic pain and for
sedation in intensive care. Heart function, breathing, and airway reflexes generally remain functional.
Effects typically begin within five minutes when given by injection with the main effects lasting up to 25
minutes

Use

Anesthesia

Uses as an anaesthetic:

 Anesthesia in children, as the sole anesthetic for minor procedures or as an induction agent
followed by muscle relaxant and tracheal intubation
 Asthmatics or people with chronic obstructive airway disease
 As a sedative for physically painful procedures in emergency departments
 Emergency surgery in field conditions in war zones
 To supplement spinal or epidural anesthesia/analgesia using low doses

Since it suppresses breathing much less than most other available anaesthetics, ketamine is used in
medicine as an anesthetic; however, due to the hallucinations it may cause, it is not typically used as a
primary anesthetic, although it is the anaesthetic of choice when reliable ventilation equipment is not
available.

Ketamine is frequently used in severely injured people. It is the drug of choice for people in traumatic
shock who are at risk of hypotension. Low blood pressure is harmful in people with severe head
injury and ketamine is least likely to cause low blood pressure, often even able to prevent it.

The effect of ketamine on the respiratory and circulatory systems is different from that of other

anesthetics. When used at anesthetic doses, it will usually stimulate rather than depress the circulatory
system. It is sometimes possible to perform ketamine anesthesia without protective measures to the
airways. Ketamine is considered relatively safe because protective airway reflexes are preserved.

Ketamine is used as a bronchodilator in the treatment of severe asthma. 

Pain management

Ketamine may be used for postoperative pain management. Low doses of ketamine
reduce morphine use and nausea and vomiting after surgery.

It may also be used as an intravenous analgesic with opiates to manage otherwise intractable pain,
particularly if this pain is neuropathic. It has the added benefit of counteracting spinal
sensitization or wind-up phenomena experienced with chronic pain. At these doses,
the psychotropic side effects are less apparent and well managed with benzodiazepines. Ketamine is an
analgesic that is most effective when used alongside a low-dose opioid; because, while it does have
analgesic effects by itself, the doses required for adequate pain relief when it is used as the sole
analgesic agent are considerably higher and far more likely to produce disorienting side effects. 
Side effects

There are known side effects that include one or more of the following:

 Cardiovascular: abnormal heart rhythms, slow heart rate or fast heart rate, high blood

pressure or low blood pressure
 Central nervous system: Ketamine is traditionally avoided in people with or at risk
of intracranial hypertension (ICP) due to concerns about ketamine causing increased intracranial
pressure. It does not increase ICP more than opioids.
 Dermatologic: Transient erythema, transient morbilliform rash
 Gastrointestinal: Anorexia, nausea, increased salivation, vomiting
 Local: Pain or exanthema of the injection site
 Neuromuscular and skeletal: Increased skeletal muscle tone (tonic-clonic movements)
 Ocular: Double vision, increased intraocular pressure, nystagmus, tunnel vision
 Respiratory: Airway obstruction, apnea, increased bronchial secretions, respiratory depression,
laryngospasm
 Other: Anaphylaxis, dependence, emergence reaction

In 10-20% of patients at anesthetic doses experience adverse reactions that occur during emergence
from anesthesia, reactions that can manifest as seriously as hallucinations and delirium.  the chance of
this occurring can be reduced by minimizing stimulation to the patient during recovery and pretreating
with a benzodiazepine, alongside a lower dose of ketamine. Patients who experience severe reactions
may require treatment with a small dose of a short- or ultrashort-acting barbiturate.

Interactions

Other drugs which increase blood pressure may interact with ketamine in having an additive effect on
blood pressure including: stimulants, SNRI antidepressants, and MAOIs. Increase blood pressure and
heart rate, palpitations, and arrhythmias may be potential effects.

Ketamine may increase the effects of other sedatives in a dose dependent manner, including, but not
limited
to; alcohols,benzodiazepines, opioids, quinazolinones, phenothiazines, anticholinergics and barbiturates

Usual Adult Dose for Anesthesia

IV:
-Induction: 1 to 4.5 mg/kg IV; alternatively, 1 to 2 mg/kg IV at a rate of 0.5 mg/kg/min; (2 mg/kg dose
provides 5 to 10 minutes of surgical anesthesia within 30 seconds)

IM:
-Induction: 6.5 to 13 mg/kg IV; (9 to 13 mg/kg IV provides 12 to 25 minutes of surgical anesthesia)