EMCrit.org

· Central adrenergic release, premedication with depressants (benzos) or fentanyl will probably blunt this response.

· Probably has neuroprotective effect by NDMA antagonism, so probably will be allowed to be used in stroke and head injury in the future.

· True laryngospasm is exceedingly rare, probably just tongue obstruction. Inevitably resolves with airway positioning.

· Glycopyrolate .01 mg/kg, not to exceed .2 mg or atropine .01 mg/kg not to exceed .5 mg (can go in same syringe as ketamine, though usually better to give 10-20 minutes beforehand)

· Benzos totally unnecessary in kids, probably not to be used for routine in adults as will prolong recovery times. Use when/if emergence reaction. Recovery period must be quiet, take off BP cuff, keep in calm environment.

Ketamine 1-2 mg/kg IV, give atropine beforehand (can go in same syringe), .5-1 mg/kg/hr infusion

Head Injury

Safety of sedation with ketamine and versed in severe head injury patients: comparison with sufentanil.
No increases in ICP, comparable to the fentanyl derivative 25 patients (Crit Care Med. 2003 Mar;31(3):711-7)

(Emergency Medicine Journal 2007;24:794-795)

Cerebral blood flow (CBF) is critically dependant on cerebral perfusion pressure (CPP) and oxygenation in acute head injuries. Optimal CPP is achieved by maintaining a normal mean arterial pressure (MAP) and limiting iatrogenic increases in intracranial pressure (ICP).1 Brain tissue has high oxygen consumption and no reserves; hypoxia therefore has rapid and profound effects. Early tracheal intubation and ventilation can help prevent hypoxia and aspiration. Hypoxia and hypotension in traumatic brain injury are associated with a 75% mortality rate.2 End tidal carbon dioxide should be maintained around 5 kPa, as hypercapnia causes cerebral vasodilation and increased ICP.3

Ketamine, a potent analgesic, can be used for dissociative anaesthesia in higher doses (2 mg/kg), or sedation in lower doses. It has a rapid onset and relatively short duration of action (5–10 min). Unlike other commonly used induction agents, ketamine does not suppress respiratory activity or airway reflexes; it also has a positive effect on gut motility, and vomiting after administration is uncommon. These properties make it the ideal agent when profound analgesia and sedation are required without a definitive airway in place.3

Ketamine causes increased catecholamine release and decreased norepinephrine (noradrenaline) re-uptake which results in increased heart rate, arterial pressure, and MAP. This makes it a useful analgesic for trauma patients who may already be haemodynamically compromised. A single episode of hypotension is associated with a worse outcome.2

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. Head injury increases concentrations of glutamate, which induces neuronal apoptosis. Ketamine blocks the actions of glutamate on the NMDA receptor, which may protect against cellular neurotoxicity, but this has yet to be demonstrated in human studies.1 3 4

Despite these benefits, the use of ketamine in patients with head injuries remains controversial. Early studies suggested that the use of ketamine may have resulted in a transient increase in ICP in a small number of patients.3 CPP was compromised only in the patients with pre-existing intracranial hypertension and obstruction to the flow of cerebral spinal fluid. This has, however, led to the persistent belief that ketamine is contraindicated in patients with traumatic head injuries. Studies done subsequently have shown, however, that the effects of ketamine on cerebral haemodynamics and ICP are in fact variable and depend on both the presence of additional anaesthetic agents and PaCO2 values.5

This patient was sedated with midazolam 10 mg iv, which prevents the emergence phenomenon, and ventilation was controlled artificially en route to hospital. When ketamine is used in the presence of controlled ventilation, in conjunction with anaesthetics which reduce cerebral metabolism such as {gamma}-aminobutyric acid (GABA) receptor agonists, ICP is not increased.1 4

1. Albanèse J, Arnaud S, Rey M, et al. Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation. Anesthesiology 1997; 87: 1328–34.[CrossRef][Medline]
2. Anon. Prehospital Trauma Life Support Committee of the National Association of Emergency Medical Technicians in Cooperation with The Committee on Trauma of The American College of Surgeons. PHTLS , 6th ed, 2007: 194–221.
3. Sehdev RS, Symmons DAD, Kindl K. Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas 2006; 18: 37–44.[CrossRef][Medline]
4. Himmelseher S, Durieux ME. Revising a dogma: ketamine for patients with neurological injury? Anesth Analg 2005; 101: 524–34.[Abstract/Free Full Text]
5. Mayberg TS, Lam AM, Matta BF et al. Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anaesthesia in patients undergoing craniotomy. Anesth Analg 1995; 81: 84–9.[Abstract]

Probably no difference with or without antisalagogue (Acad Emerg Med. 2003;10:482-483.)

Purpose
d To define the guidelines for patient selection, administration, monitoring,
and recovery for ED dissociative sedation.
Definition of Dissociative Sedation
d A trancelike cataleptic state induced by the dissociative agent ketamine,
characterized by profound analgesia and amnesia, with retention of
protective airway reflexes, spontaneous respirations, and cardiopulmonary
stability.
Characteristics of the Ketamine ‘‘Dissociative State’’
d Dissociation: After administration of ketamine, the patient passes into
a fugue state or trance. The eyes may remain open, but the patient does
not respond.
d Catalepsy: Normal or slightly enhanced muscle tone is maintained. On
occasion, the patient may move or be moved into a position that is selfmaintaining.
Occasional muscular clonus may be noted.
d Analgesia: Analgesia is typically substantial or complete.
d Amnesia: Total amnesia is typical.
d Maintenance of airway reflexes: Upper airway reflexes remain intact and
may be slightly exaggerated. Intubation is unnecessary, but occasional
repositioning of the head may be necessary for optimal airway patency.
Suctioning of hypersalivation may occasionally be necessary.
d Cardiovascular stability: Blood pressure and pulse rate are not decreased
and typically are mildly increased.
d Nystagmus: Nystagmus is typical.
Indications
d Short, painful procedures, especially those requiring immobilization (eg,
facial laceration, burn debridement, fracture reduction, abscess incision
and drainage, central line placement, tube thoracostomy).
d Examinations judged likely to produce excessive emotional disturbance
(eg, pediatric sexual assault examination).
Contraindications: Absolute (Risks Essentially Always Outweigh Benefits)
d Age younger than 3 months (higher risk of airway complications)
d Known or suspected psychosis, even if currently stable or controlled with
medications (can exacerbate condition)
Contraindications: Relative (Risks May Outweigh Benefits)
d Aged 3 to 12 months (higher risk of airway complications)
d Procedures involving stimulation of the posterior pharynx (higher risk of
laryngospasm)
d History of airway instability, tracheal surgery, or tracheal stenosis
(presumed higher risk of airway complications)
d Active pulmonary infection or disease, including upper respiratory infection
or asthma (higher risk of laryngospasm)
d Known or suspected cardiovascular disease, including angina, heart
failure, or hypertension (exacerbation due to sympathomimetic properties
of ketamine). Avoid ketamine in patients who are already hypertensive
and in older adults with risk factors for coronary artery disease.
d Head injury associated with loss of consciousness, altered mental status,
or emesis (elevated intracranial pressure with ketamine)
d Central nervous system masses, abnormalities, or hydrocephalus (elevated
intracranial pressure with ketamine)
d Glaucoma or acute globe injury (elevated intraocular pressure with ketamine)
d Porphyria, thyroid disorder, or thyroid medication (enhanced sympathomimetic
effect)
Personnel
d Dissociative sedation is a 2-person procedure, 1 (eg, nurse) to monitor the
patient and 1 (eg, physician) to perform the procedure. Both must be
knowledgeable about the unique characteristics of ketamine.
d Avoid dissociative sedation when personnel are not experienced with
ketamine or may not have time to perform such sedation properly.
Presedation
d Perform a standard presedation assessment
d Educate accompanying family about the unique characteristics of the
dissociative state, especially if they will be present during the procedure
or recovery.

Emergence Reaction

Malviya S, Voepel-Lewis T, Ramamurthi R, Burke C, Tait AR. Clonidine for the prevention of emergence agitation in young children: efficacy and recovery profile. Pediatric Anesthesia 2006; 16: 554–9.

Study results were published in the August issue of the Archives of General Psychiatry.

"The public health implications of being able to treat major depression this quickly would be enormous," said NIH Director Elias A. Zerhouni, M.D. "These new findings demonstrate the importance of developing new classes of antidepressants that are not simply variations of existing medications."

For this study 18 treatment-resistant, depressed patients were randomly assigned to receive either a single intravenous dose of ketamine or a placebo (inactive compound). Depression improved within one day in 71 percent of all those who received ketamine, and 29 percent of these patients became nearly symptom-free within one day. Thirty-five percent of patients who received ketamine still showed benefits seven days later. Participants receiving a placebo infusion showed no improvement. One week later, participants were given the opposite treatment, unless the beneficial effects of the first treatment were still evident. This "crossover" study design strengthens the validity of the results.

57 S.M. Green and J. Li, Ketamine in adults: what emergency physicians need to know about patient selection and emergence reactions [editorial], Acad Emerg Med 7 (2000), pp. 278–281. Abstract + References in Scopus | Cited By in Scopus

Ketofol

Ketofol (1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was administered intravenously at the discretion of
the treating physician by using titrated aliquots. [Ann Emerg Med. 2007;49:23-30.]

Etomidate

(4) Dursteler BB, et al. Etomidate-facilitated hip reduction in the emergency department Acad Emerg Med 2000;7: 1165-6.

(5) Frymann SJ, et al. Reduction of dislocated hip prosthesis in the emergency department using conscious sedation: a prospective study Emergency Medicine Journal 2005;22:807-809

low dose versed (0.015 mg/kg) given 90 sec before etomidate attenuates the myoclonus and doesn't prolong time to recovery. (Anesth Analg 2007;105:1298)

Propofol

Initial bolus: Various Guidelines say 0.5 to 2 mg / kg bolus. I would recommend sticking with the lower end 0.5-1 mg/kg To make it even easier just give 50 mg bolus to an average size adult; The recommendations on drip rates are all over the place ranging from 10 mcg/kg/min to 200 mcg/kg/min.
I think 10 mcg/kg/ min is too low and a more reasonable starting dose is 100 mcg/kg/min and then titrate upwards by 20 mcg/kg/min every 5 min. I saw one protocol by GI docs for colonoscopy which started at 140 mcg/kg/min. If they can started at 140 mcg/kg/min without complications then I feel confident that our ED docs can start at 100 mcg/kg/min and deliver safe sedation.

So to summarize give 0.5-1 mg/kg bolus (50 mg is fine for most adults) followed by a drip at 100 mcg/kg/min. Titrate upward by 20 mcg/kg/min q 5 min.

(Academic EM 10:9 931-937, Sept 2003)
Randomized Clinical Trial of Propofol versus Methohexital for Procedural Sedation during Fracture and Dislocation Reduction in the Emergency Department: 1 mg/kg then 0.5 mg/kg Q 3-5 minutes

Propofol (2,6-diisopropylphenol), an oil in water emulsion, is an intravenous agent that is used for induction and maintenance of anesthesia.7 Propofol, like benzodiazepines, inhibits activity at both the spinal and supraspinal synapses by interacting with and potentiating the GABA-mediated receptors.8,9 However, it does not potentiate GABA-evoked currents through the benzodiazepine site.10 When combined with flurazepam, the potentiation of GABA receptor activity obtained with propofol is greater than expected from a simple additive response.

Intravenous injection of propofol produces a rapid hypnosis, usually by 40 seconds after the start of a bolus injection. Maintenance of sedation (25 to 75 µg/kg/minute) or anesthesia (100 to 200 µg/kg/minute) can be achieved by continuous intravenous infusion titrated to clinical effect.7 Propofol distributes very rapidly throughout the body including the brain. The pharmacokinetic profile of propofol is described by a three-compartment model:

Propofol Infusion Syndrome

Often seen in kiddies, but reported in adults (Burow BK - Anesthesiology - 01-JUL-2004; 101(1): 239-41 followed by
editorial comment)

Green Urine is Seen

The desired clinical response can be titrated by either bolus injections of 0.5 mg/kg every 10 seconds to a total dose of 2 to 2.5 mg/kg or by continuous infusion.

Although hypotension is the most commonly reported adverse event, volume loading with 12 mg/kg of Ringer’s lactate solution is effective in maintaining hemodynamic stability.18 Interestingly, propofol in high doses has also been rarely reported to cause seizures, but the mechanism is unknown.19,20

Annals EM Dec 2003 42:6; 793. propofol recovery time is 5-15 minutes with a 30 second onset

Bassett Peds Study-hypoxia in 5%, airway repositioning in 2% and apnea needing BVM in .8%

Great review of lit

Propofol (2,6 di-isopropylphenol) is a very short acting non-opioid sedative–hypnotic agent. It is thought to work by potentiating the binding of -amino butyric acid to receptor sites in the central nervous system (CNS).6 It has no analgesic properties and must be used in conjunction with adequate pain relief. Studies vary regarding the extent of amnesic properties compared to benzodiazepines.6,7 but it has recognised antiemetic and euphoric effects. Onset of action is <60 seconds (one arm–brain circulation). Despite a half life of 13–44 hours, duration of action is approximately 10 minutes, owing to rapid redistribution from CNS tissue to muscle and fat. Metabolic clearance equals or exceeds hepatic blood flow, suggesting extrahepatic clearance, possibly pulmonary.6 Pharmacokinetics are unaffected by renal or hepatic disease but dose reduction is required in the elderly,6 as volume of distribution falls with age.

Bassett et al19 (table 1) is a further study in the same institution following almost the same protocol. Patients were fasted for 3 hours and 10 litres of oxygen was administered routinely. At least three deviations from protocol were noted when patients were not given oxygen, and all of these patients became hypoxic.

Propofol (9) vs. Etomidate (9) vs. Midazolam (8) vs. Midazolam with flumazenil (6)

Recovery Etomidate 9.5 minutes, Midazolam 21 minutes, Propofol 8 minutes, Midaz c flumaz 3 minutes but high resedation rate

It has substantial inhibitory effects on sympathetic activity and reflex responses to hypotension

Study using infusion instead of injection (Am J Emerg Med. 2006 Sep;24(5):599-602)

Because of propofol's lack of analgesic activity, fentanyl was given intravenously at a dose of 2 μg/kg approximately 2 minutes before beginning the propofol infusion. Propofol was then begun as an infusion using a pump. Initially, a loading infusion of 0.21 mg kg−1 min−1 was given until the patient was sedated to an appropriate level, assessed by the attending emergency physician. At this point, the procedure was started, and the propofol infusion was switched to a maintenance rate of 3-6 mg kg−1 h−1, at the attending physician's discretion, until the procedure was completed. A table with appropriate doses and drip rates was compiled and available at all times during the procedure

Etomidate and propofol appear equally safe for ED procedural sedation; however, etomidate had a lower rate of procedural success and induced myoclonus in 20% of patients. (Annals of Emergency Medicine Volume 49, Issue 1 , January 2007, Pages 15-22)

Anaesthesia
Volume 62 Issue 7 Page 690Issue 7 - 701 - July 2007
To cite this article: P. C. A. Kam, D. Cardone (2007)
Propofol infusion syndrome

Propofol infusion syndrome (Anaesthesia 62 (7), 690–701.)

Xenon

May have potential as an inhalational sedative without hemodynamic side effects (Crit Care Med 2003 31:10)

We can sedate the critically ill, unstable patient (Acad Emerg Med 2005;12(2):124)

0.5 mg/kg of propofol plus 0.5µg/kg of remifentanil, given intravenously over 60 and30 seconds, respectively for shoulder dislocation (EMJ 2006;23:57-58)

Propofol

Etomidate

redistribution from brain to peripheral tissues accounts for its short action, though eventual metabolism is by liver

nitroglycerin like effect on heart fx paitents which reduces ventricular filling

ativan and versed essentially have the same dosing with 2 of either = to about 5 of valium

ativan has no active metabolites, diazepam and versed do. Kidney fx will cause prolonged action

needles have 45 degree non cutting points to increase tactile sensation. use 22 g to increase injection sensation and backflow of art blood

ETCO2

ETCO2 monitoring makes procedural sedation safer (Acad Emerg Med Volume 13, Number 5 500-504)

Class 1	Healthy patient, no medical problems
Class 2	Mild systemic disease
Class 3	Severe systemic disease, but not incapaitating
Class 4	Severe systemic disease that is a constant threat to life
Class 5	Moribund, not expected to live 24 hours irrespective of operation
An e is added to the status number to designate an emergency operation. An organ donnor is usually designate as Class 6

Procedural Sedation

ASA Classification

Fasting

Peds

Ketamine

Head Injury

Emergence Reaction

Ketofol

Etomidate

Propofol

Propofol Infusion Syndrome

Great review of lit

Xenon

Propofol

Etomidate

ETCO2