Sometimes IV sedation and analgesics will be combined with other types of pain control — such as local anesthesia, which involves one or more injections to numb a small area of the body, or regional anesthesia, which numbs a larger part of the body, such as from the waist down. A physician anesthesiologist is a medical doctor who specializes in anesthesia, pain management, and critical care medicine.

Physician anesthesiologists are highly skilled medical experts. Skip to content. It has a large volume of distribution secondary to its lipophilicity, while its clearance correlates most closely with pharmacokinetic mass similar to lean body mass ; therefore, significant drug accumulation and a prolonged context sensitive half-life can occur with prolonged infusions.

Remifentanil, a derivative of fentanyl, is unique as an opioid secondary to its metabolism by nonspecific blood and tissue esterases. It is utilized primarily as an infusion 0. Dosing regimens for the infusion should be based on ideal body weight or lean body mass, 17 and hypotension and bradycardia are the most common side effects seen with remifentanil administration.

Importantly and secondary to its ultra-short half-life, supplemental analgesic medication is required at the conclusion of a remifentanil infusion.

The selection of an opioid for systemic analgesia has traditionally depended on the pharmacology of the specific opioid and the likely required duration. Unfortunately, few comparative trials have been performed in critically ill patients. Remifentanil provided better outcomes than morphine with regards to time at optimal arousal level, necessity of supplemental sedation, duration of mechanical ventilation, and extubation time in one randomized double blind study.

With regards to acute brain dysfunction outcomes, the literature is inconsistent. In a prospective cohort study of elderly hip fracture patients, the patients who received higher morphine equivalents per day were less likely to develop delirium than patients who received less analgesic medications.

Sedative medications are commonly prescribed within the ICU environment primarily for the treatment of agitation and anxiety, which themselves may be caused by many different conditions eg, dyspnea, delirium, mechanical ventilation, lack of sleep, and untreated pain. The appropriate use of sedatives can facilitate patient care and contribute to patient safety; however, their use is associated with both short- and long-term negative patient outcomes, including prolonged mechanical ventilation and cognitive dysfunction.

There are many ICU arousal scales which are used to provide goal directed therapy individualized to the patient. It is important to recognize that the arousal scales are not applicable when the patient is being administered neuromuscular blocking drugs, and consideration should be given to the use of the Bispectral Index monitor in those instances. Delirium is an acute fluctuating change in mental status characterized by inattention and altered levels of consciousness that is now considered to be a presentation of brain organ dysfunction.

Sedation protocols are commonplace within ICU environments and provide a structured framework that guides sedative administration and monitoring. Their use alone has been associated with significantly improved patient outcomes. Key elements of sedation protocols should include arousal monitoring instruments, sedative dosing instructions, spontaneous awakening trials that are linked to spontaneous breathing trials, and early mobilization therapy.

Spontaneous awakening trials daily interruption of sedation have been shown to reduce duration of mechanical ventilation, decrease ICU length of stay, and decrease the incidence of PTSD.

Despite numerous studies demonstrating that deep sedation is not required in the majority of ICU patients and that lighter sedation goals improve outcomes, many providers have been hesitant to implement these techniques due to concern for patient safety and the belief that patients would be more likely to develop long-term psychological issues without deep sedation during their ICU stay. The ABC trial, however, showed no difference in the rate of re-intubation between the control and intervention groups, and studies incorporating daily wake up trials have shown no increase in the incidence of PTSD.

It is advisable that each ICU develop a local sedation protocol that takes into account current research, patient characteristics, and local evidence.

Prior to implementation, all staff involved in administering the protocol should be trained in its application and opportunity given for modification when necessary. Providers should recognize that sedative medications are considered part of a multimodal approach to ensuring patient comfort and safety.

Important aspects also include providing analgesia, maintenance of a normal day—night cycle, patient positioning, and appropriate mechanical ventilation strategies. It must also be appreciated that sedatives should only be considered once pain has been adequately treated — the concept of analgesia-based sedation or analgosedation. Once analgesia has been obtained, sedative medications can be utilized to reach arousal targets when needed.

An empiric protocol Figure 1 for the management of pain, sedation, and delirium is provided as a reference. With permission from www. The ideal sedative will be inexpensive, have minimal respiratory depression, elimination independent of organ function, short context sensitive half-life, and no active metabolites. Unfortunately, none of the commonly used sedatives fulfill all these criteria, and practitioners should be aware of their limitations when choosing a sedative medication.

The most common sedative medications used within the ICU are propofol, dexmedetomidine, and benzodiazepines, with other agents such as clonidine, ketamine, volatile anesthetics, and neuromuscular blockers used as adjunct therapies.

Importantly, the duration of sedative medication administration has been shown to correlate with the duration of mechanical ventilation, and the consistent theme throughout many sedation studies is that efforts should be made to minimize the total dose of sedative by using the minimum effective dose, daily interruption of sedation, and infusions for the shortest time required.

It has proven utility as a sedating agent in the ICU due to its rapid onset 1—2 minutes and short duration of action 2—8 minutes. Its volume of distribution is large with a short distribution half-life.

Emergence is related to redistribution and not metabolic clearance when used as bolus or low-dose infusion, which can be advantageous in patients with renal or hepatic dysfunction.

When propofol is used as a long-term infusion and saturation of peripheral tissues occurs, emergence is more related to metabolic clearance. Propofol side effects include hypotension due to vasodilation and myocardial depression, respiratory depression, and hypertriglyceridemia. The hypertriglyceridemia may either be due to the intralipid carrier or altered hepatic lipid metabolism, which can be seen with the propofol infusion syndrome PRIS. When high dosage or prolonged infusions are being used, it is recommended to regularly monitor serum pH, lactate, creatinine kinase, triglyceride levels, and electrocardiograms Brugada-type changes.

Dexmedetomidine is an alpha-2 receptor agonist whose site of action includes presynaptic neurons in the locus ceruleus and spinal cord. It causes sedation and analgesia without significant respiratory depression. Dexmedetomidine is metabolized by the liver, and patients with severe liver disease require lower dosing, whereas there is no need for dose adjustment in those with renal dysfunction.

Benzodiazepines have been used for sedation for many years within the ICU setting with midazolam, lorazepam, and diazepam being the most commonly utilized agents. They are GABA agonists metabolized in the liver to active metabolites lorazepam being the exception with no active metabolite.

These metabolites can lead to prolongation of their sedative effects, especially in the presence of renal failure. The use of lorazepam is limited by the fact it is dissolved in propylene glycol, which can accumulate to produce metabolic acidosis and renal dysfunction. Despite the widespread use of benzodiazepines for sedation in the ICU, there is a growing body of evidence that shows that they are associated with poorer patient outcomes, including increased brain dysfunction, time on mechanical ventilation, and ICU length of stay.

Analgesia-based sedation is a concept that has been around for many years but which has had resurgence with lighter sedation techniques and the development of opioid medications with rapid onset and offset.

In a randomized controlled study comparing analgesia only remifentanil with propofol rescue versus analgesia and sedation titrated propofol or benzodiazepine infusion with as-needed opioid , the analgesia only group had decreased ICU length of stay, more days without mechanical ventilation, and improved Sedation-Agitation Scores. As discussed earlier, there are limited data to suggest a single superior analgesic drug for analgosedation regimens.

Therefore, the decision on which analgesic agent to employ should be based upon clinical conditions and cost, with the agent titrated using validated scales. When compared with benzodiazepines, propofol has been shown to increase duration at target arousal level, reduce cost per patient, and decrease time spent on mechanical ventilation. Subgroup analysis of the MENDS study showed improved outcomes in septic patients, including increased survival, with dexmedetomidine use.

A study comparing dexmedetomidine and propofol sedation in post-surgical patients showed similar time at target sedation, but patients sedated with dexmedetomidine required less supplemental analgesia. In a recently published study, dexmedetomidine was compared to midazolam MIDEX and propofol PRODEX for light to moderate sedation in patients requiring mechanical ventilation for greater than 24 hours.

Arousability, communication, and patient cooperation were improved with dexmedetomidine sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam, and time to extubation was faster in the dexmedetomidine groups than either the midazolam or propofol groups. Overall, length of ICU and hospital stay and mortality were similar between groups. The most often discussed concerns with dexmedetomidine are bradycardia and cost.

Future studies comparing outcomes, including cost, between propofol and dexmedetomidine are necessary to further delineate their potential advantages and disadvantages in different ICU patient populations.

Clonidine is an alpha-2 agonist similar to dexmedetomidine; however, its clinical effects are altered secondary to differing affinity for the receptor. Clonidine can provide a low level of sedation and analgesia, and its main uses within the ICU tend to be for withdrawal syndromes eg, alcohol withdrawal or rapid discontinuation of analgesic or sedative medications.

Ketamine is an N -methyl- D -aspartate antagonist and should be considered an adjunctive sedative agent. It possesses analgesic properties and is often used in burn patients to facilitate opioid reduction.

Recently, however, there has been evidence of potential neuroprotective effects with ketamine, leading some to include a recommendation that it be used in conjunction with a GABA agonist in patients with traumatic brain injury.

Volatile anesthetic use for sedation within the ICU setting has been limited by problems with atmospheric pollution, administration, and ICU culture.

With increasing evidence of the harm associated with deep sedation techniques, the utilization of neuromuscular blockade as an adjunct in the sedation of critically ill patients has decreased considerably. Pharmacologic paralysis remains utilized in patients with progressive respiratory failure and high peak inspiratory pressures unresponsive to conventional ventilation and in patients with postoperative open abdomens.

Cardiac monitoring is recommended as it may cause Q-T prolongation and an increased incidence of arrhythmias.

Chlorpromazine has similar indications and mechanism of action as haloperidol. Thus, chlorpromazine has a much wider profile of possible adverse effects. It is less sedative than haloperidol with a greater incidence of respiratory depression, and is rarely administered in ICU. Benzodiazepines produce sedation and hypnosis by modulating the effects of GABA, the main inhibitory neurotransmitter within the central nervous system. Benzodiazepines may be administered as bolus doses or by continuous infusion.

They cause less haemodynamic compromise than i. Concerns with their use include dependence and withdrawal agitation. Midazolam is metabolized in the liver to active compounds. It has the highest clearance of the benzodiazepines rendering it most suitable as an infusion 0. It is often used as a bolus method of producing sedation 1—4 mg p. Diazepam is metabolized in the liver to active compounds.

It has the lowest clearance of the benzodiazepines and its half-life is greatly increased by use as an infusion. It is not commonly used in ICU for sedative purposes. It can be given orally 2 mg three times daily or i. Opioids are commonly used to provide analgesia, narcosis, and anxiolysis.

Side-effects include respiratory depression, bradycardia, and hypotension secondary to histamine release. They stimulate the chemoreceptor trigger zone and may cause nausea and vomiting via 5HT 3 and dopamine receptors.

Opioids also inhibit peristalsis precipitating constipation. The use of the relatively new ultra-short-acting opioid remifentanil is increasing, and this merits further discussion. It has a highly predictable onset and offset, with a stable context sensitive half-time 3—10 min.

Studies have shown a shorter duration of mechanical ventilation and quicker ICU discharge with remifentanil compared with other opioids. An infusion rate of 0. If adequate sedation is not achieved at 0. Because of the very quick offset of analgesia, an alternative analgesic drug should be given before withdrawal of the infusion if pain is still likely.

It is particularly useful if agitation is a feature or after withdrawal of benzodiazepines or opioids. In addition to its central nervous system effects, it may also cause significant haemodynamic changes. This includes an initial rise in arterial pressure, which is later followed by a more prolonged fall. Bradycardia may occur due to a reduction in sympathetic tone and an increase in vagal tone. After abrupt withdrawal, acute rebound hypertensive crises have been reported.

Clonidine has an elimination half-life of 8. Neuromuscular blocking agents do not provide sedation, and are only occasionally used in critical care due to concerns about chronic muscle weakness and the risk of paralysis without adequate sedation. Development of myopathy is directly related to duration of infusion.

Sedative agents can be administered as boluses when required usually as determined by the nurse looking after the patient , or by continuous infusion. The latter is most common, providing a constant level of sedation with less chance of intermittent agitation. However, a continuous infusion of sedation has been identified as an independent predictor of a longer duration of mechanical ventilation and a longer stay in the intensive care unit and in the hospital.

Target sedation scores should be set and re-evaluated on a regular basis. This allows therapy to be titrated appropriately, to achieve the desired response, and should therefore prevent over and under-sedation as the clinical needs of the patient change.

A typical sedation pathway, based on the Intensive Care Society Guidelines A sedation holiday involves stopping the sedative infusions and allowing the patient to wake.

The infusion should only be restarted once the patient is fully awake and obeying commands or until they became uncomfortable or agitated and deemed to require the resumption of sedation.

Ideally, this should be performed on a daily basis. This strategy has been shown to decrease the duration of mechanical ventilation and the length of stay in ICU, without increasing adverse events such as self-extubation. Sleep is defined as a natural periodic state of rest for the mind and body, in which the eyes usually close and consciousness is completely or partially lost, so that there is a decrease in bodily movement and responsiveness to external stimuli. It is an important component in the recovery from critical illness and deprivation may impair tissue repair and overall cellular immune function.

However, sleep quantity and quality can be difficult to achieve in an ICU environment. These patients will first of all say on a ventilator longer, because they have to be cleared mentally in order to get the endotracheal tube pulled out.

And so by staying on a ventilator longer, this put them at risk for ventilator associated pneumonia and all of the other complications that come from being bedridden in an ICU, not getting up early enough and ambulating, so a lot of these things. And delirium in particular, patients would stay delirious and agitated for days on end sometimes.

Interviewer: Well, that was something I wanted to talk about. Something I find interesting is that benzodiazapine more frequently causes delirium and patients with long bouts of delirium are more likely to have an extended hospital stay or even die.

I'm wondering what the link is between delirium and these terrible outcomes? Richard Barton: There have been associations in other studies, other situations, showing that delirium, which is really altered thought, almost like psychosis, that delirium is associated with not only poor immediate outcomes, but with actual decrease in mental function, if you will, over the long term.

In other words, you don't want to be delirious for long periods of time. It literally seems to permanently alter brain function. Interviewer: And is it the delirium that directly harms the individual, or is the delirium an indicator that something else is wrong? Richard Barton: I think that's an excellent question, and I'm not sure that I know the answer.

Nick Lonardo: Do you know what? There is no answer. We don't know. We simply don't know. We know that the duration of delirium that we see in the ICU is strongly independently associated with increased six month mortality.