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Sedation

There has been a general consensus that moderate sedation (formerly conscious sedation) provides adequate control of pain and anxiety for the overwhelming majority of routine endoscopic procedures as well as adequate amnesia.
Over 50% of adverse reactions during endoscopy are cardio-respiratory, mostly related to over dosage of sedation. A 2004 report by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD), “Scoping our Practice”, found that there had been 1,818 deaths after therapeutic GI endoscopic procedures. NCEPOD advisors judged that the sedation given was inappropriate in 14% of cases, usually because an overdose of benzodiazepine had been administered.

What is moderate(conscious) sedation?

  • A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation
  • No interventions are required to maintain a patent airway and spontaneous ventilation is adequate
  • Cardiovascular function is usually maintained.

What are the common drugs/regimes used?
The most commonly used regimens are midazolam with pethidine, midazolam with fentanyl and midazolam alone. Key aspects in the use of these agents are that the sedative effects are dose related, and that there is substantial synergism between narcotics and benzodiazepines.
Pethidine has a superior synergistic effect with midazolam with regard to sedation when compared with fentanyl.
Discuss the pharmacological properties of the sedative agents used for endoscopy?
Pharmacological properties of sedative agents used for endoscopy (1, 2)

Sedative Onset of action(min) Duration of action Elimination half life Metabolism/excretion
Midazolam 1-2.5 2-6h 1.8-6.4h Hepatic and intestinal: excreted in urine
Pethidine 5 2-4h 2-7h Hepatic; excreted in urine
Fentanyl ≤1.5 1-2h 2-7h Hepatic; excreted in urine

Discuss the use of reversal agents for opioid and benzodiazepines?
Narcotics can be reversed by the administration of naloxone. The main contraindication to the use of naloxone is chronic use of narcotics, in which naloxone can precipitate acute narcotic withdrawal, including severe hypertension and pulmonary oedema. Midazolam and diazepam can be reversed by the administration of flumazenil. Flumazenil is contraindicated in patients with seizure disorders and those on chronic benzodiazepine therapy.
How are the doses titrated?
A key principle in the administration of sedative agents is that drugs must be titrated in incremental doses to a desired sedative effect. The dose needed to achieve adequate sedation is difficult to predict because the pharmacological response of individual patients to specific agents is variable (the range of individual responses is three- to fivefold)
The British Society of Gastroenterology (3) recommends that 5 mg of Midazolam should usually be the maximum dose given and that doses in excess of Pethidine 50mg or fentanyl 100 mcg are seldom required. In the case of patients over the age of 70 years, the BSG suggests an average dose of no more than 2 mg of midazolam. Should an opioid such as pethidine be required, as it frequently is for procedures such as ERCP or colonoscopy, then the BSG recommends that the opioid be given first (because of its delayed onset of action) and then the benzodiazepine given slowly and cautiously. In the case of pethidine, the BSG has suggested an average dose of no more than 25 mg in a patient over the age of 70 years of age.

How to sedate difficult patients?
Patients occasionally become restless or even violent following sedation.  This situation can sometimes be salvaged by reversing the sedation which may allow the endoscopy to proceed but when such difficulty can be anticipated general anaesthesia is usually the best option.

Alcoholics and regular benzodiazepine users are notoriously difficult to sedate and their response may be unpredictable or even paradoxical on occasions.  In these circumstances the prior administration of an opioid can be useful.
PS- It is recommended that patients who have been sedated with an IV benzodiazepine do not drive a car, operate machinery, sign legal documents or drink alcohol for 24 hours. This is irrespective of whether their sedation has been reversed with flumazenil.
References

  1. Roseveare C, Seavell C, Patel P, et al. Patient-controlled sedation and analgesia, using propofol and alfentanil, during colonoscopy: a prospective randomized controlled trial. Endoscopy 1998; 30: 768–73.
  2. Rudner R, Jalowiecki P, Kawecki P, Gonciarz M, Mularczyk A, Petelenz M. Conscious analgesia/sedation with remifentanil and propofol versus total intravenous anesthesia with fentanyl, midazolam, and propofol for outpatient colonoscopy. Gastrointest Endosc 2003; 57: 657–63.
  3. http://www.bsg.org.uk/clinical-guidelines/endoscopy/guidelines-on-safety-and-sedation-during-endoscopic-procedures.html

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