Conscious Sedation: A How-to Guide

The term conscious sedation is used to describe the act of giving medications to alleviate anxiety and/or pain associated with potentially unpleasant procedures. The term "twilight sleep" was used to describe a pre-anaesthetic state often used in the setting of palliative care. With the advent of potent and relatively short acting compounds, it is much easier to render a patient into a "twilight sleep". However even these newer drugs are not without their pitfalls. This article will briefly review the agents used in conscious sedation, potential traps and strategies employed to avoid these.

The Setting

While conscious sedation is relatively safe on the whole, there continues to be incidental and isolated reports of complications and even fatalities associated with this practice. The unfortunate aspect of all of these are that a common sense protocol would avoid the majority of them. The Canadian Anaesthetist's Society has developed guidelines for delivery of "anaesthesia" outside of the O.R. which are very straight forward.

Sedation should be administered by persons familiar with the drugs used and prepared to deal with any potential complications. This also means the setting of administration must be equipped with an oxygen source, airway management equipment, drugs to treat both anaphylaxis and other forms of hypotension, and appropriate monitors. Monitoring should include attendance by a physician or experienced nurse and a minimum of oxygen saturation - this gives information on heart rate, output, and oxygenation. The important point here is that monitoring should not cease after the procedure has been completed - this may even by the time of greatest risk. At this time the patient has circulating sedatives and respiratory depressants but no longer has any noxious stimuli to maintain an awake state. The patient must have intravenous access not only to administer the sedation but also to treat potential complications - the last thing you want to do with a "flat", apneic patient is to struggle to re-establish an intravenous.

Following administration of sedation the patient must not be left unattended until they have reached a comfortable level of "wakefulness". There have been many reports of deaths in emergency department waiting rooms and radiology suites following the completion of the procedure performed.

The Drugs

The majority of physicians are familiar with the "workhorses" of conscious sedation - benzodiazipines and narcotics. Other drugs less commonly used but effective include sedative-hypnotics, neuroleptics and anaesthetic agents. The remainder of this paper will briefly review their use, their risks and - perhaps most importantly - antagonists one should be familiar with.

There are a variety of benzodiazepines on the market but here we will talk about diazepam (Valium), lorazepam (Ativan), and midazolam (Versed). While others are available, their delivery systems and pharmacodynamic profiles make them inappropriate for modern conscious sedation.

Diazepam is a relatively inexpensive, lipid insoluble compound with a relatively fast onset of action- within 5 minutes- but unpredictable duration of action. In most healthy persons one would expect its iv actions to subside in 1 to 2 hours but due to the presence of active metabolites this can be prolonged in the elderly or those with hepatorenal impairment. Due to its chemical nature, diazepam evokes pain on injection which lead to the development of Diazemules - combining diazepam with an intralipid base. This also significantly increased the cost. At doses of 0.07 to 0.15 mg/kg IV one can expect about 65 to 70% of patients to experience amnesia of events. Diazepam should not be given im due to its local irritation which can even result in local tissue necrosis.

Lorazepam is another inexpensive compound of increased potency vs. diazepam. It may be delivered sublingually as well as PO, IM, and IV. Intravenously it again has a relative fast onset of action - within 5 minutes - but has a longer duration of action - 3 to 4 hours - and even longer in the elderly. It does not have active metabolites and this fact along with cost has lead to its resurgence as a sedative in the ICU. At doses of 0.02 to 0.04 mg/kg IV one can expect approximately 75 to 85% of patients to experience amnesia.

Midazolam is one of the newer agents available with a potency between lorazepam and diazepam. It can be given SC, IM or IV. In certain situations it may also be given PO although one will not find that in the CPS. Its chemistry is interesting as it is hydrophilic in the bottle but exposure to blood pH makes it lipophillic. This allows a slightly faster onset of action - 2 to 3 minutes - without pain on injection. Due to its chemistry again one can expect a short duration of action - 1 to 2 hours - even in the elderly. Problems with midazolam include cost, the impression of an increased incidence of disinhibition and combativeness and an ability to exaggerate the respiratory depressant effects of narcotics. In anaesthesia this became known as co-induction but in the US it was responsible for enough deaths in endoscopy suites that the FDA considered withdrawing the drug. It was these deaths that lead to the development of monitoring guidelines. Doses for midazolam IV should be 0.02 to 0.04 mg/kg. In adults I prefer to give 2 mg every 2 to 3 minutes until a suitable level of sedation is reached or a total dose 0.1 mg/ kg is reached. On an added note, oral midazolam is now being touted as a premedication and sedative in the paediatric population. In this situation the dose is 0.3 mg/kg PO with a maximum dose of 7.5 mg. A warning, the drug tastes awful so it is useful to disguise it in acetaminophen 15 mg/ kg which is a taste the children usually recognize and accept.

The next commonly used family of medications for conscious sedation are the opiates. Despite a long history, opiates are still used inappropriately at times and newer, potentially better, drugs are not utilized due to unfamiliarity. This article will touch on three commonly used drugs - morphine, meperidine and fentanyl. One should add that narcotics should be reserved for procedures associated not only with anxiety but with pain.

Morphine, a naturally occurring compound, has been available in various forms for over a thousand years and has served as a chemical template for those drugs that have followed. It is relatively hydrophillic which accounts for a slight delay in its onset of action (comparatively) but also accounts for its longer duration of action. In doses of 0.07 to 0.15 mg/kg one can expect an effect within 5 to 10 minutes but its duration of action can be two hours or even more. It can cause histamine release due to direct stimulation of mast cells by the drug causing an anaphylactoid reaction in its extreme. The drug is emetogenic but the effect is delayed and seems to occur two to three hours later.

Meperidine (Demerol) is a semi-synthetic compound with a slightly faster onset of action compared to morphine but a shorter duration of action. The doses given range from 0.3 to 0.7mg/ kg results in onset of action under 5 minutes with a duration of action of one to two hours. It causes histamine release to a similar extent as morphine but it causes much more nausea immediately as compared to morphine. Almost all patients given meperidine will need some form of anti-emetic.

Fentanyl (Sublimaze) is a synthetic lipohyllic compound with a quicker onset and shorter duration of action than morphine or meperidine. It is very potent and cause less histamine release and less emesis than those other compounds. The drawback to fentanyl, aside from cost, is its narrow therapeutic window - the difference between sedative/ analgesic levels and respiratory depressant levels is much less than with the previously mentioned drugs. This problem is even more exaggerated when benzodiazipines are used. Doses of 0.3 to 0.5 mcg/kg should be given followed by 0.1mcg/kg until an adequate level of sedation is reached. One should not use more than 1 mcg/ kg unless they are prepared to deal with airway consequences. It has an onset of action in 2 to 5 minutes in most patients and its duration of action is about one hour in most cases. It has no significant metabolites (as does meperidine) and was initially favoured due to its cardiovascular stability. With experience, this is probably the drug of choice for conscious sedation involving narcotics.

At this point one should mention the newer synthetic agents. Sufentanil (Sufenta) and alfentanil (Alfenta) are potent, highly lipophillic agents with rapid - under two minutes- onset of action and short duration of action - 30 to 60 minutes. They are very expensive - 3 and 6 times more per ampule than fentanyl respectively - but more importantly their therapeutic window is extremely narrow and the incidence of respiratory depression is high. The newest agent is remifentanyl (Ultiva) with an onset within 1 to 2 minutes and a duration of action of only 10 to 15 minutes. This agent, at the present time is being marketed only as a general anaesthetic agent and its use outside of the OR, other than by anaesthetists, cannot be recommended at this time.

One class of medications that are often neglected when considering sedation are the neuroleptics. These can be particularly helpful in dealing with combative or confused patients in whom you are concerned about respiratory depression from opiates or potential dis-inhibition by benzodiazepines. Two drugs worth considering are haloperidol (Haldol) and droperidol (Inapsine). These can safely be given intravenously with an onset of action of about 5 to 7 minutes. Of the two, haloperidol causes less cardiovascular instability as IV boluses of droperidol can cause marked hypotension particularly in the dehydrated. The description "neurolept" anaesthetic was applied to a technique based on neuroleptics and opiates to provide general anaesthesia - so popular was this at one time that a drug named Innovar was marketed which was a combination of fentanyl and droperidol. The technique fell into disfavour with the development of newer agents and due to the fact patients did not appreciate the sensations provided by the drug. It is still useful, however, on occasion.

When using neuroleptics the same basic tenants apply- blood pressure, pulse oxygenation, and level of consciousness must all be monitored. With droperidol I use 1 mg boluses every 3 to 5 minutes to a maximum of 5 mg. At this point I might add a small amount of narcotic such as fentanyl 50 to 100 mcg. With haloperidol a similar dosing regime is useful although I might start with an initial bolus of 2 mg but then supplement with 1 mg every 3 to 5 minutes. The major problem with neuroleptics is the development of dystonia - a generalized stiffness. Other side effects include akasthesia but also the more worrisome occulogyric crisis. These may all be treated with Cogentin which appears to be more effective im rather than iv. The worst case scenario is the development of Neuroleptic Malignant Syndrome which mimics the anaesthetists worst nightmare of malignant hyperthermia. This is a life threatening complication and Dantrolene is indicated in its emergency treatment along with active cooling, arrhythmia management, ventilatory support and ICU admission.

The last class of drugs used for conscious sedation are the anaesthetic induction agents. These include propofol (Diprivan), ketamine (Ketalar) and sodium thiopentone (Pentothal). They are however used mostly by anaesthetists and so will not be discussed in this article.

When one strays too far with conscious sedation one should be familiar with too drugs that can help you and potentially save a patient. Most people are familiar with naloxone (Narcan) as an opiate antagonist, however its use in oversedation is slightly different than neonatal resuscitation or in the treatment of the unconscious patient in OPD. First, for it to be effective, opiates should have been used as part of the conscious sedation "cocktail". Secondly the dosage regime is slightly different in the awake but drowsy patient- one can start by diluting 0.4mg in a 10cc syringe. One may then administer 0.04mg boluses every 2 to 4 minutes until a desired effect is seen. Naloxone is not an entirely innocuous drug as doses of 0.4 mg have resulted in arrhythmias, pulmonary edema and death.

One should also be familiar with flumazenil (Annexate) with is a GABAminergic antagonist which means it reverses the effects of the benzodiazepines. Flumazenil has been available for the past five years but still is not as popular as naloxone. Its real role likely resides in reversing the "co-induction" between opiates and benzodiazepines. Recommended dosages are 0.1 mg every five minutes up to three doses or in the unconscious patient 0.3 mg every 5 minutes up to three doses. Flumazenil is relatively contraindicated in patients with a history of seizure disorders as it lowers seizure threshold and can precipitate a seizure. It should also be used in caution in patients with habitual or frequent benzodiazepine use as its administration can initiate a withdrawal phenomena.

Summary

Conscious sedation is a safe practice in a setting with proper monitoring, adequate IV access, and experienced personnel. The physician administering the medications should be familiar with them and prepared to deal with their potential side-effects. One should establish a "comfort zone" that they will accept in conscious sedation and once that level is reached one more experienced in such matters such as an anaesthetist should be consulted. The patient will thank you for alleviation of discomfort and anxiety but no thanks will be received for hypoxia and injury. Finally an emergency is not a good time to get acquainted with an unfamiliar drug so I would always suggest getting advice from an experienced colleague.

- Peter MacNeil

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For more information.

Conscious Sedation: A How-to Guide The term conscious sedation is used to describe the act of giving medications to alleviate anxiety and/or pain associated with potentially unpleasant procedures. The term "twilight sleep" was used to describe a pre-anaesthetic state often used in the setting of palliative care. With the advent of potent and relatively short acting compounds, it is much easier to render a patient into a "twilight sleep". However even these newer drugs are not without their pitfalls. This article will briefly review the agents used in conscious sedation, potential traps and strategies employed to avoid these. The Setting While conscious sedation is relatively safe on the whole, there continues to be incidental and isolated reports of complications and even fatalities associated with this practice. The unfortunate aspect of all of these are that a common sense protocol would avoid the majority of them. The Canadian Anaesthetist's Society has developed guidelines for delivery of "anaesthesia" outside of the O.R. which are very straight forward. Sedation should be administered by persons familiar with the drugs used and prepared to deal with any potential complications. This also means the setting of administration must be equipped with an oxygen source, airway management equipment, drugs to treat both anaphylaxis and other forms of hypotension, and appropriate monitors. Monitoring should include attendance by a physician or experienced nurse and a minimum of oxygen saturation - this gives information on heart rate, output, and oxygenation. The important point here is that monitoring should not cease after the procedure has been completed - this may even by the time of greatest risk. At this time the patient has circulating sedatives and respiratory depressants but no longer has any noxious stimuli to maintain an awake state. The patient must have intravenous access not only to administer the sedation but also to treat potential complications - the last thing you want to do with a "flat", apneic patient is to struggle to re-establish an intravenous. Following administration of sedation the patient must not be left unattended until they have reached a comfortable level of "wakefulness". There have been many reports of deaths in emergency department waiting rooms and radiology suites following the completion of the procedure performed. The Drugs The majority of physicians are familiar with the "workhorses" of conscious sedation - benzodiazipines and narcotics. Other drugs less commonly used but effective include sedative-hypnotics, neuroleptics and anaesthetic agents. The remainder of this paper will briefly review their use, their risks and - perhaps most importantly - antagonists one should be familiar with. There are a variety of benzodiazepines on the market but here we will talk about diazepam (Valium), lorazepam (Ativan), and midazolam (Versed). While others are available, their delivery systems and pharmacodynamic profiles make them inappropriate for modern conscious sedation. Diazepam is a relatively inexpensive, lipid insoluble compound with a relatively fast onset of action- within 5 minutes- but unpredictable duration of action. In most healthy persons one would expect its iv actions to subside in 1 to 2 hours but due to the presence of active metabolites this can be prolonged in the elderly or those with hepatorenal impairment. Due to its chemical nature, diazepam evokes pain on injection which lead to the development of Diazemules - combining diazepam with an intralipid base. This also significantly increased the cost. At doses of 0.07 to 0.15 mg/kg IV one can expect about 65 to 70% of patients to experience amnesia of events. Diazepam should not be given im due to its local irritation which can even result in local tissue necrosis. Lorazepam is another inexpensive compound of increased potency vs. diazepam. It may be delivered sublingually as well as PO, IM, and IV. Intravenously it again has a relative fast onset of action - within 5 minutes - but has a longer duration of action - 3 to 4 hours - and even longer in the elderly. It does not have active metabolites and this fact along with cost has lead to its resurgence as a sedative in the ICU. At doses of 0.02 to 0.04 mg/kg IV one can expect approximately 75 to 85% of patients to experience amnesia. Midazolam is one of the newer agents available with a potency between lorazepam and diazepam. It can be given SC, IM or IV. In certain situations it may also be given PO although one will not find that in the CPS. Its chemistry is interesting as it is hydrophilic in the bottle but exposure to blood pH makes it lipophillic. This allows a slightly faster onset of action - 2 to 3 minutes - without pain on injection. Due to its chemistry again one can expect a short duration of action - 1 to 2 hours - even in the elderly. Problems with midazolam include cost, the impression of an increased incidence of disinhibition and combativeness and an ability to exaggerate the respiratory depressant effects of narcotics. In anaesthesia this became known as co-induction but in the US it was responsible for enough deaths in endoscopy suites that the FDA considered withdrawing the drug. It was these deaths that lead to the development of monitoring guidelines. Doses for midazolam IV should be 0.02 to 0.04 mg/kg. In adults I prefer to give 2 mg every 2 to 3 minutes until a suitable level of sedation is reached or a total dose 0.1 mg/ kg is reached. On an added note, oral midazolam is now being touted as a premedication and sedative in the paediatric population. In this situation the dose is 0.3 mg/kg PO with a maximum dose of 7.5 mg. A warning, the drug tastes awful so it is useful to disguise it in acetaminophen 15 mg/ kg which is a taste the children usually recognize and accept. The next commonly used family of medications for conscious sedation are the opiates. Despite a long history, opiates are still used inappropriately at times and newer, potentially better, drugs are not utilized due to unfamiliarity. This article will touch on three commonly used drugs - morphine, meperidine and fentanyl. One should add that narcotics should be reserved for procedures associated not only with anxiety but with pain. Morphine, a naturally occurring compound, has been available in various forms for over a thousand years and has served as a chemical template for those drugs that have followed. It is relatively hydrophillic which accounts for a slight delay in its onset of action (comparatively) but also accounts for its longer duration of action. In doses of 0.07 to 0.15 mg/kg one can expect an effect within 5 to 10 minutes but its duration of action can be two hours or even more. It can cause histamine release due to direct stimulation of mast cells by the drug causing an anaphylactoid reaction in its extreme. The drug is emetogenic but the effect is delayed and seems to occur two to three hours later. Meperidine (Demerol) is a semi-synthetic compound with a slightly faster onset of action compared to morphine but a shorter duration of action. The doses given range from 0.3 to 0.7mg/ kg results in onset of action under 5 minutes with a duration of action of one to two hours. It causes histamine release to a similar extent as morphine but it causes much more nausea immediately as compared to morphine. Almost all patients given meperidine will need some form of anti-emetic. Fentanyl (Sublimaze) is a synthetic lipohyllic compound with a quicker onset and shorter duration of action than morphine or meperidine. It is very potent and cause less histamine release and less emesis than those other compounds. The drawback to fentanyl, aside from cost, is its narrow therapeutic window - the difference between sedative/ analgesic levels and respiratory depressant levels is much less than with the previously mentioned drugs. This problem is even more exaggerated when benzodiazipines are used. Doses of 0.3 to 0.5 mcg/kg should be given followed by 0.1mcg/kg until an adequate level of sedation is reached. One should not use more than 1 mcg/ kg unless they are prepared to deal with airway consequences. It has an onset of action in 2 to 5 minutes in most patients and its duration of action is about one hour in most cases. It has no significant metabolites (as does meperidine) and was initially favoured due to its cardiovascular stability. With experience, this is probably the drug of choice for conscious sedation involving narcotics. At this point one should mention the newer synthetic agents. Sufentanil (Sufenta) and alfentanil (Alfenta) are potent, highly lipophillic agents with rapid - under two minutes- onset of action and short duration of action - 30 to 60 minutes. They are very expensive - 3 and 6 times more per ampule than fentanyl respectively - but more importantly their therapeutic window is extremely narrow and the incidence of respiratory depression is high. The newest agent is remifentanyl (Ultiva) with an onset within 1 to 2 minutes and a duration of action of only 10 to 15 minutes. This agent, at the present time is being marketed only as a general anaesthetic agent and its use outside of the OR, other than by anaesthetists, cannot be recommended at this time. One class of medications that are often neglected when considering sedation are the neuroleptics. These can be particularly helpful in dealing with combative or confused patients in whom you are concerned about respiratory depression from opiates or potential dis-inhibition by benzodiazepines. Two drugs worth considering are haloperidol (Haldol) and droperidol (Inapsine). These can safely be given intravenously with an onset of action of about 5 to 7 minutes. Of the two, haloperidol causes less cardiovascular instability as IV boluses of droperidol can cause marked hypotension particularly in the dehydrated. The description "neurolept" anaesthetic was applied to a technique based on neuroleptics and opiates to provide general anaesthesia - so popular was this at one time that a drug named Innovar was marketed which was a combination of fentanyl and droperidol. The technique fell into disfavour with the development of newer agents and due to the fact patients did not appreciate the sensations provided by the drug. It is still useful, however, on occasion. When using neuroleptics the same basic tenants apply- blood pressure, pulse oxygenation, and level of consciousness must all be monitored. With droperidol I use 1 mg boluses every 3 to 5 minutes to a maximum of 5 mg. At this point I might add a small amount of narcotic such as fentanyl 50 to 100 mcg. With haloperidol a similar dosing regime is useful although I might start with an initial bolus of 2 mg but then supplement with 1 mg every 3 to 5 minutes. The major problem with neuroleptics is the development of dystonia - a generalized stiffness. Other side effects include akasthesia but also the more worrisome occulogyric crisis. These may all be treated with Cogentin which appears to be more effective im rather than iv. The worst case scenario is the development of Neuroleptic Malignant Syndrome which mimics the anaesthetists worst nightmare of malignant hyperthermia. This is a life threatening complication and Dantrolene is indicated in its emergency treatment along with active cooling, arrhythmia management, ventilatory support and ICU admission. The last class of drugs used for conscious sedation are the anaesthetic induction agents. These include propofol (Diprivan), ketamine (Ketalar) and sodium thiopentone (Pentothal). They are however used mostly by anaesthetists and so will not be discussed in this article. When one strays too far with conscious sedation one should be familiar with too drugs that can help you and potentially save a patient. Most people are familiar with naloxone (Narcan) as an opiate antagonist, however its use in oversedation is slightly different than neonatal resuscitation or in the treatment of the unconscious patient in OPD. First, for it to be effective, opiates should have been used as part of the conscious sedation "cocktail". Secondly the dosage regime is slightly different in the awake but drowsy patient- one can start by diluting 0.4mg in a 10cc syringe. One may then administer 0.04mg boluses every 2 to 4 minutes until a desired effect is seen. Naloxone is not an entirely innocuous drug as doses of 0.4 mg have resulted in arrhythmias, pulmonary edema and death. One should also be familiar with flumazenil (Annexate) with is a GABAminergic antagonist which means it reverses the effects of the benzodiazepines. Flumazenil has been available for the past five years but still is not as popular as naloxone. Its real role likely resides in reversing the "co-induction" between opiates and benzodiazepines. Recommended dosages are 0.1 mg every five minutes up to three doses or in the unconscious patient 0.3 mg every 5 minutes up to three doses. Flumazenil is relatively contraindicated in patients with a history of seizure disorders as it lowers seizure threshold and can precipitate a seizure. It should also be used in caution in patients with habitual or frequent benzodiazepine use as its administration can initiate a withdrawal phenomena. Summary Conscious sedation is a safe practice in a setting with proper monitoring, adequate IV access, and experienced personnel. The physician administering the medications should be familiar with them and prepared to deal with their potential side-effects. One should establish a "comfort zone" that they will accept in conscious sedation and once that level is reached one more experienced in such matters such as an anaesthetist should be consulted. The patient will thank you for alleviation of discomfort and anxiety but no thanks will be received for hypoxia and injury. Finally an emergency is not a good time to get acquainted with an unfamiliar drug so I would always suggest getting advice from an experienced colleague. - Peter MacNeil