Primer

Analgesics and Sedatives in ICU

The sedation protocols must be ingrained in such a way that they should not prolong the ICU stay or mechanical ventilation

Critically ill patients are a unique group of patients, who require large doses of analgesics, sedatives and relaxants, but have a reduced tolerance to these drugs due to the seriousness of their medical condition, trauma and unstable haemodynamics. The priority in critically ill patients is resuscitation. Therefore, the administration of the above mentioned drugs takes a lower priority and gets minimal attention. However, the increased awareness of untreated pain and sedation in the Intensive Care Units (ICU) has lead to a major change in the attitude of intensivists in the management of these problems. In order to treat, one should understand the pathophysiology thoroughly. When pain is controlled both therapeutically and by technological advances it certainly leads to demonstrable reductions in the incidence of pain and thereby patient comfort and safety.

Pain-Analgesia-Analgesic Drugs

Pain should be relieved at all costs, on humanitarian, ethical, medical and probably on financial grounds. First and foremost recognise that patients are in pain and diagnose why they are in pain. Pain is of two types, nocioceptive due to tissue injury and trauma; neuropathic, which could be due to primarily lesion or dysfunction in the nervous system.

Let us examine why pain is rated much less in an ICU. Firstly, the patient is critical and primary concern is saving life. Secondly, patients and physicians concern in giving opioids for fear of addiction, weaning from ventilation and haemodynamics instability. Technological advances of infusion pumps, Patient Controlled Analgesia (PCA), high nurse-patient ratio as well as better monitoring techniques to assess the cardio-respiratory function in a continuous manner, has led to the belief that pain can be relieved much better in an ICU set-up. However it does not happen all the time.

The next hindrance is the assessment of pain in a sedated and paralysed patient. This can lead to under estimation of the pain. The medico legal implications are also one of the causes for under diagnosing pain. Now, it is a general agreement that as long as primary motivation is giving analgesia for pain relief, then actions are ethically justified, despite any secondary effect of the drug.

What Causes Pain in ICU?

Besides patient's own nocioceptive or neuropathic mechanisms there are many areas, which cause discomfort to the patients. Tracheal intubation, catheter placements, tube placement, suctioning, physiotherapy, dressing changes are all painful. A number of patients complained that chest tube placement and removal are very painful. Peripheral intravenous potassium and some anaesthetic drugs are painful. The adverse effects of pain, affects all the systems in the body.

Opioids for Pain Management

Patient controlled analgesia

Opioids are mainstay of analgesics in the ICU. All available drugs from Morphine to Sufentanil are used either as bolus, continuous infusion or PCA. The minimal effective analgesic concentration varies with each drug and requires adequate titration and is patient specific. They mainly act at the opioid receptor for analgesia but have some side effects.

NSAIDs

This class of drugs is a heterogeneous group mainly consisting of organic acid. They have an opioids sparing effect. They have both central and peripheral sites of analgesic activity. The use of such drugs in critically ill is controversial. The complications like renal failure, gastric bleeding, make them less suitable for patients in ICU.

Patients in ICU have altered sleep patterns. Therefore it may be rational to use tricyclic antidepressant drugs particularly if pain is thought to be neuropathatic. Alternative therapies like TENS, acupuncture need not be withheld if they are beneficial, as they reduce the requirements of opioid or other analgesic drugs.

Regional Anaesthesia

Use of local anaesthetics applied topically infiltration, plexus or specific block, intrathecal or extradural have all been tried. Autonomic blockade attenuates the stress response, leads to an improved respiratory function and skeletal muscle relaxation.

Extradural Analgesia

Paravertebral block

In specific group of patients the use of Lumbar Epidural (LEA) or Thoracic Epidural (TEA) has shown to be beneficial. Sick patients undergoing major surgeries have been able to demonstrate a decrease in postoperative complications and improved outcome. Yager et al has shown significantly lower complication rates in high-risk patients undergoing abdominal surgery. Lower incidence of cardiovascular failure and major infections compared with controls that received opioids. TEA showed less complications following thoraco-abdominal oesophagogastrectomy for oesophageal cancer. Post-operative epidural analgesia may reduce the overall incidence of major infections by a number of mechanisms. It may be due to the fact that they spend less time in ICU, may be extubated early, obtundation of stress response, thereby immune-competence is retained. The over all time spent is ICU is reduced so that risk of nosocomial infections and sepsis are reduced.

Peripheral Nerve Blocks

The use of continuous nerve block for femur has been reported. Positioning becomes easy. Continuous brachial plexus block is used to provide analgesia, decrease vasospasm and promote collateral circulation in upper limb injury. Nerve blocks are integral part of anaesthesia and postoperative pain management but their use in critically ill patients is limited.

Intra Pleural Analgesia

Infusion pumps

It has been used for fractured ribs, but there are potential problems with leakage of local anaesthetic in to chest drain. High toxic levels of local anaesthetics occur. Improved outcome in critically ill patients is doubtful. Inter costal block, along with catheterisation and infusion of local anaesthesia has been successfully utilised in patients with head injury and multiple rib fractures. This may be a method of choice over extradural analgesia as an inadvertent dural puncture in a patient with raised ICP is disastrous.

In summary, relief of pain is of utmost importance. It can reduce the ICU stay and make the procedures in ICU more comfortable. Pain is of complex nature in ICU setting. Anxiety and depression should be treated with adjuvant drugs. Selection of extradural analgesia for certain subsets of patients is very beneficial. Use of alternative methods of pain relief should be looked into. NSAIDs should be used with extreme caution.

Sedation in ICU

Sedation in operating room meets specific goals, whereas that in ICU has few absolute indications or end points. The role of sedation and paralysis in ICU is an adjunct to facilitate other treatment modalities. Therefore, the goal of sedation is to have a cooperative and reasonably calm patient who will not harm himself or interfere with ICU care. Mental status has to be assessed on a regular basis and the mobility is also important. Therefore, the sedation in ICU follows different rules to that of in the operating room. The use of sedatives is further complicated by the side effects that are very important in critically ill patients. Tolerance to sedatives drugs, hypotension, impairment of ventilatory drive, which can lead to delayed weaning, bowel hypomortility, and idiosyncratic reactions are few common complications. Therefore, it is mandatory to use sedatives judiciously in titrable doses. The goals have to be well defined. Use of sedations score may be beneficial in the assessment.

Indications for sedation are:

• Anxiety and fear.
• Sleep.
• Increased metabolism.
• Protection against myocardial ischemia.
• Amnesia during muscle paralysis.
• Control of agitation.
• Facilitate mechanical ventilation.
• Control status epilepsy.
• Status asthamaticus.
• Control of intra cranial pressure and
• Tetanus poisoning.

Indicators for Sedatives

The most important indication for the use of sedative drugs is to improve oxygenation and reduce peak airway pressure. Facilitation of mechanical ventilation definitely needs both muscle relaxants and sedatives at least in the early periods of shock, disseminated intra-vascular coagulation, multi-organ dysfunction, pesticide poisoning and head injury. Introduction of assisted modes of ventilation has greatly reduced the need for heavy sedation and paralysis. However the use of pressure control and inverse ratio ventilation has once again increased the need for sedation and muscle paralysis.

Drugs

The common drugs used for sedation in ICU are benzodiazepines and propofol. These are intravenous hypnotics, which modulate the r-aminobutyric acid type A receptor. The first benodiazepine used in ICU could be the use of diazepam for procedures like cardioversion and as muscle relaxant for tetanus. They are widely used because of their anxiolytic and hypnotic properties. At sedative doses midazolam (<0.1mg/kg) decreases tidal volume by approximately 40 per cent with a compensatory increase in respiratory rate resulting in no change in resting minute volume. Midazolam has no venous irritation, is short acting, and does not accumulate in patients with normal renal function. There is no increased risk of bradycardia, blood stream infection, and hypertriglyceredemia. There is no excitation of the central nervous system.

Short-term sedation

Any benzodiazipine can be utilised as intramuscular injection, expect diazepam. They are reasonably well tolerated. However, more predictable effects are with intermittent, Intra-Venous (IV) boluses. For short-term sedation there are no clinically proven pharmacokinetic or pharmacodynamic benefits of one IV benzodiazipine over the other. The choice relates to familiarity of use and cost. However, most ICUs prefer to use midazolam and more recently propofol.

Long-term sedation

This means patient gets sedation for more than 24 hours. Therapeutically, that drug with long duration of the action and that, which does not accumulate is ideally suited. With intermittent boluses there are peaks and valleys in drug concentration. Accurate infusion pumps deliver continuous IV infusions. Midazolam has attractive pharmacokinetics, which make it useful as a continuous infusion. Some reported prolong sedation even after midazolam. It is being re-evaluated in ICU environment. Tolerance and dependences are recognised during the use of continuous IV benzodiazepine. They are also useful in treatment of alcohol withdrawal.

Propofol

Introduced as anaesthetic induction agent in late 1980s, it has gained widespread use in anaesthesiology. Onset of action is rapid. It is isopropyl phenol highly lipid soluble Crosses blood brain barrier. It has pain on injection. Reduces systemic blood pressure due to a combination of vasodilatation and cardiac depression. Slight decrease in heart rate is noted. Recovery is rapid. First use in ICU was by Grounds in 1987. Propofol gained popularity in cardiac surgical patients for 'fast track' in which the goal is rapid extubation.

The pharmcokinetics of propofol have been extensively studied. Used in lower dosages, the recovery is rapid. It is redistributed, has high clearance rate of 1.5 to 2.1 L/min. This exceeds hepatic blood flow. There are no effects on its kinetics by the kidney. Increasing or decreasing the infusion rate will have predictable effect on depth of sedation. This linear relationship between pharmacokinetics and dynamics gives it a simple profile of titrability in the ICU.

The drug also gives nursing and medical staff the ability to lighten the patient's level of sedation during family visits. It can be easily increased for any procedures like catheter placements and suctioning etc. Increase in lipid levels is a concern. Strict aseptic precautions should be undertaken when delivering the drug, as its rich medium is ideal for rapid growth of microorganisms. Propofol can be cost effective if titrated correctly. Several studies have shown cost saving compared to midazolam infusions. Use of unit base sedation scales such as Ramsay sedation scale can reduce the cost of sedation.

Neuroleptics

They are antipsychotics. Droperidol crosses blood-brain barrier. Exhibits a sedative and antiemetic effect, additive to analgesic effects of narcotics. 1.25 to 2.5mg intravenous bolus is used in conjunction with analgesics. 2.5 to 5mg can be given intravenously before any procedure.

Haloperidol: It is similar to droperidol in structure. Crosses blood-brain barrier. Has diffuse depressive effect at several subcortical levels. In patients who are agitated or exhibit ICU psychosis can be given in doses of 1 to 5mg intravenously. Useful in alcohol withdrawal also.

In a clinical investigation to find out the type of sedatives used in European ICUs the authors formatted a questionnaire, which revealed that the use of sedation scores varies from 72 per cent in UK to 18 per cent in Austria. Midazolam was used in 63 per cent and Propofol in 35 per cent. Opioid usage for analgesia was as follows: Morphine was used 33 per cent, Fentanyl 33per cent and Sufentanil 24 per cent. Multi-variate analysis showed Midazolam and Fentanyl as the most common combination used.

Data from 27 trails were analysed. The average duration of sedation varied from four to 339 hours. In 10 trails, the duration of adequate sedation was longer with propofol. There was a lack of evidence in difference in weaning times. Arterial hypotension and triglyceridemia were occurred more often with Propofol. There was a lack of evidence of superiority of high compliance with ICU sedation guidelines promoting Lorazepam rather than Midazolam or Propofol in mechanically ventilated patients led to a 75 per cent decrease in sedation drug costs and did not adversely affect the clinicians' ability to wean patients from mechanical ventilation. Whatever the sedation used, it should suit the needs of the patients. The sedation protocols must be ingrained in such a way that they should not prolong the ICU stay or time mechanical ventilation

Dexmedetomidine is a potent new alpha-2 adrenoceptor agonist with an alpha-2 to alpha- ratio more than seven times that of Clonidine. Its potent sedative, analgesic and sympatholytic effects blunt the cardiovascular responses (hypertension, tachycardia) without unexpected toxicity. Many reports confirmed its pharmacological properties, if given by infusion. Recent report confirmed favourable non-depressant effect on respiration and cardiovascular stability. It also confirmed the sparing effect on the use of analgesics which indicates its analgesic effect. The sedation quality is unique in the sense that the patient can be easily awakened. It is becoming a very popular drug for sedation in ICU.

The writer is Head, Department of Anaesthesiology & Intensive CareYashoda Hospital Hyderabad
manimalarao@hotmail.com