Pain relief and sedation in the intensive care unit

Pain Relief and Sedation in the Intensive Care Unit Duraiyah Thangathurai, Maged Mikhail, Kenneth Kuchta, and Peter Roffey

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,AIN, fear, and anxiety are common and often overlooked problems in patients in the intensive care unit (ICU). Holland et al 1 have shown that sedative and pain medications are often prescribed to satisfy the expectations of the medical staff or to provide a convenient nursing condition rather than in response to the actual needs and fears of the patient? Pain, fear, and anxiety influence many aspects of the physician-patient relationship. Appropriate relief is often associated with amelioration of the patient's complaints even if the underlying disease is not controlled. Historically, even before the advancement of Western medicine, pain and discomfort have concerned every patient and physician and every attempt was taken to alleviate them, frequently without much success. Despite major advances in technology, pharmacology, and pain management techniques, pain in the ICU patient remains largely underevaluated and poorly treated. Discomfort, pain, fear, anxiety, and sleep deprivation result in physiologic and psychological stress with important sequelae. TM Hemodynamic disturbances from catecholamine release may be manifested as hypertension, tachycardia, and cardiac arrhythmias. A neuroendocrine stress response increases production of adrenocorticoid hormones (corticotropin, cortisol, and aldosterone), angiotensin, antidiuretic hormone, and catecholamines, resulting in hyperglycemia, protein catabolism, fluid retention, and electrolyte disturbances. The negative protein balance can lead to poor wound healing and a depressed immune response. The circadian rhythm is reversed, leading to further neuroendocrine and sleep disturbances, s-7 Psychological consequences of pain include insomnia, depression, anxiety, and psychosis. s-t~ It is not surprising that the posttraumatie stress disorder is increasingly reported among patients with the adult respiratory distress syndrome who have been on ventilators. Moreover, patients who are placed on high doses of opiates and benzodiazepines often subsequently develop acute withdrawal states.

PROBLEM AREAS IN CRITICALLY ILL PATIENTS Evaluating Pain and Anxiety

The inability to evaluate pain is a major problem in the management of ICU patients. Critically ill patients are often too ill to verbalize their feelings or perception of pain. Patients on ventilators have a minimal ability to communicate, especially if muscle relaxants are used for paralysis. Their sensorium is frequently altered by delirium and confusion, making evaluation difficult. Psychosomatic symptoms may be the only manifestations of pain in the ICU patient; as a result, patients may pull intravenous catheters, tubes, and drains and fight the ventilator. Although widely practiced, the use of restraints and muscle relaxants to control these symptoms is not a good alternative to proper pain management. Inadequate pain control was found in more than 70% of medical intensive care patients.l I Less than half of these patients were given adequate doses of pain medications. Physicians often underestimate effective dose ranges for analgesics, overestimate their duration of action, and exaggerate the dangers of addiction even if doses are within therapeutic ranges. Other investigators have found both inadequate amounts of analgesics prescribed and inadequate dosing intervals for the small amounts prescribed. 12"13 Two additional recent studies have found that ICU nurses often failed to assess and manage pain appropriately, even when clear indications and appropriate doses of analgesics are ordered. 14,15 Intensive Care Unit Protocols

Many ICUs use protocols for pain relief and sedation. Extremely ill patients may not tolerate the medications and doses required in these proto-

From the Department of Anesthesia, Universityof Southern California School of Medicine, Los Angeles, CA. Address reprint requests to Duraiyah Thangathurai, MD, Intensive Care Unit, Kenneth Norris, Jr, CancerHospital, 1441 Eastlake, Room 441, Los Angeles, CA 90033. Copyright 9 1999 by W.B. Saunders Company 0277-0326/99/1801-0007510.00/0

Seminars in Anesthesia, PerioperativeMedicine and Pain, Vol 18, No 1 (March), 1999: pp 81-86

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82 cols. These patients may be hemodynamically sensitive to pain regimens, yet continue to experience intense pain. Morphine, although widely used, may not be the best analgesic in all circumstances because of vasodilation and respiratory depression. Similarly, hypovolemic and hypotensive patients may not tolerate the symptholytic effects of epidural local anesthetic protocols.

Priority of Care Pain relief is typically not the highest priority for ICU personnel and is often overlooked because other areas of medical care are perceived to be of more importance. Hemodynamic monitoring and support, manipulation of respiratory parameters on high-tech ventilators, and other monitors often take precedence over the patient's pain and feelings.

Attitudes Pain management in most ICUs reflects the attitude of the clinicians and nursing staff. Effective pain management may not be achieved if the clinician feels comfortable with only one pharmacologic regimen. While some centers continue to manage pain with intramuscular morphine, many medical centers have begun to adopt more aggressive methods for analgesia. In the United States, intensivists most often come from an internal medicine background and are typically cardiologists or pulmonologists with limited expertise in pain management. They have strict protocols so that the nurses can carry out the orders without much understanding of the pharmacology of analgesics or exposure to alternative pain relief techniques. This approach often results in inappropriate therapy and inadequate pain relief. Despite the increasing variety and widespread availability of analgesics and newer techniques, pain management is often not altered according to the current state of an often rapidly changing patient. An intensivist that is well-versed in pain management and willing to evaluate the patient's pain and sedation requirements on a minute-tominute basis is needed. The implications of other therapies on pain management and vice versa can only be fully appreciated by an intensivist-pain management expert.

Psychological Implications Patients in the ICU often suffer from psychological and emotional disturbances as a result of pre-

THANGATHURAI ETAL existing conditions, disease states, drugs, or imbalance of the neuroendocrine system. Posttraumatic stress syndrome is increasingly recognized in ICU patients. Anxiety, depression, and psychosis are common yet underdiagnosed; unfortunately, these states can have a major psychological impact on the patient and family, s-l~ We have often seen patients with advanced directives not admitted to the ICU or intubated for ventilatory support because of a prior terrifying experience for the patient or a family member in an ICU.

Role of Pain Specialists Pain management is a relatively new specialty that focuses primarily on the treatment of acute and chronic pain in an ambulatory setting. These specialists often do not understand the complexity of critically ill patients. Successful management of the ICU patient's pain and sedation requirements demands that the clinician have not only a clear grasp of pain management concepts but also a fundamental comprehension of critical care medicine. It also requires a constant presence to frequently monitor the patient with regard to changing pain requirements and appropriately modifying techniques to changing hemodynamic, cardiac, and neurologic status.

Economic Concerns A major thrust of cost-reduction measures in many hospitals has been minimizing the number of fully trained and experienced ICU nurses because ICU staffing accounts for one of the largest components of expenditures for hospitals. The end result of this policy has been a reduction of time spent on direct patient care and, consequently, the frequency of nursing assessments. The remaining ICU-trained nurses are forced to merely scan too many patients for possible problems and concentrate on acute crisis interventions. Buzzwords such as "re-engineering" often translate into merely eliminating or overburdening the most qualified nursing personnel without evaluating the impact on patient care. The lack of training for these newly defined nursing roles and responsibilities only emphasizes the poor design of such restructuring efforts. These changes at the bedside have even greater impact if physicians rely on routine protocols for pain management. The end result can be a delay in noting a mismatch of the pain technique to the patient's condition.

PAIN RELIEF& SEDATION IN THE ICU PAIN RELIEF TECHNIQUES Intravenous Analgesics

Analgesic requirements vary greatly within and between different types of ICU patients. Postoperative, cancer, and trauma patients generally require more aggressive pain relief compared with medical patients who are on ventilators. Ongoing stress, as well as previous opioid tolerance or addiction, can significantly modify the pain threshold. Opiates are the most frequently used drugs for pain relief. Naturally occurring opiates (namely, morphine) are still more popular than synthetic drugs such as meperidine.* Morphine may be administered by intermittent intravenous boluses, continuous intravenous infusion, or epidural infusion. Patient-controlled analgesia is useful in appropriate patients with a clear sensorium. Morphine requirements vary greatly. Renal, cardiac, and hepatic impairment can significantly alter the pharmacokinetics of morphine. Its major side effect is respiratory depression. Hypotension and increased fluid requirements can occur secondary to venodilatation and histamine release. Paralytic ileus is also a common problem. Pupillary reflexes are affected and can confuse evaluation of neurosurgical patients. Morphine also can cause biliary spasm. Respiratory depression can delay weaning from the ventilator. Short-acting synthetic narcotics such as fentanyl, sufentanil, alfentanil, and remifentanil can be used as alternatives to morphine. They offer potent analgesia with a short duration of action and are therefore ideal for use as continuous infusions. Marked respiratory depressant effects, however, can limit their use in patients who are not intubated. They are therefore most suitable for patients on ventilators. Bradycardia also may be troublesome in some patients. Remifentanil is increasingly being used in the ICU because of its very short duration of action, but its cost has limited widespread use. Epidural and Other Regional Techniques

Regional techniques are most popular Ln the acute postoperative and trauma settings. The most

* Editor's note: Because of the metabolicbreakdown product, nor-meperidine, it is the editor's belief that meperidine should not be used for analgesia in the ICU. Nor-meperidine can cause convulsion,which cannot be treatedby naloxone.

83 commonly used local anesthetics are lidocaine and bupivacaine. Ropivacaine is increasingly used because of reduced cardiac toxicity compared with bupivacaine. Lumbar epidural analgesia is typically used for patients who have had abdominal surgery. Thoracic epidural infusions are useful in patients who have chest and upper abdominal incisions and those with rib trauma. Intrapleural or intercostal catheters can also provide effective analgesia in many of these patients. The combination of local anesthetics with morphine, fentanyl, or sufentanil can provide effective pain relief in more dilute concentrations than when used alone in the epidural space. Delayed respiratory d6pression and CO 2 retention are more common with water-soluble opiates, such as morphine, and are due to diffusion from the epidural space into cerebrospinal fluid and cephalad spread to the respiratory center in the brain stem. Acute respiratory depression may be observed with all epidural opiates due to systemic absorption. Moderate respiratory depression can be treated with low-dose naloxone or doxapram infusions without significantly affecting analgesia. Other side effects include nausea, vomiting, pruritus, and urinary retention. Regional analgesic techniques are contraindicated in patients with coagulation disorders, severe spinal disorders, and sepsis. Coagulation disorders are common in the ICU and may be due to thrombocytopenia, disseminated intravascular coagulation, massive blood transfusion, or sepsis; thus, the role of regional techniques in patients with these disorders is limited. Ketamine and Ketamine Mixtures

Ketamine has amnesic, sedative, and analgesic properties. It also is a bronchodilator and mild respiratory stimulant. Psychotomimetic manifestations, its major side effect, are attenuated by the addition of midazolam and possibly opioids. Opioids, such as fentanyl, in small doses potentiate ketamine's analgesic effect. Continuous intravenous analgesic mixtures containing ketamine are especially useful for patients with moderate to severe pain who have contraindications to regional anesthesia. Ketamine may be combined with midazolam and/or fentanyl. The addition of midazolam is useful in patients with significant anxiety and opioid tolerance; it also provides amnesia for patients receiving mechanical ventilation. In septic patients, ketamine has been shown to lower kinins

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and tumor necrosis factor levels. It also may have brain-protective effects via blockade of N-methylD-aspartate receptors; ketamine therefore may be useful in patients who have suffered a cardiac arrest or who are at risk of developing hypotension and hypoxemia.

dose range. Propofol's principal advantage is that its effects usually dissipate within 1 hour after the infusion is stopped. Withdrawal is rare, but has been reported following prolonged infusion. Etomidate was used in the past, but adrenocortical suppression has severely limited its use.

SEDATION Sedation may be required in patients who suffer from significant anxiety, restlessness, and confusion. Patients in the ICU exhibiting psychomotor agitation frequently pull at endotracheal tubes, chest tubes, drains, and intravascular catheters. Careful sedation helps control these symptoms. Patient discomfort and complaints may appear trivial to ICU personnel, but often are very worrisome to patients. Small doses of opioids may be used as sedatives, especially for patients on ventilators, but their prolonged use can lead to addiction, tolerance, ileus, and immunosuppression. Moreover, a withdrawal state can be precipitated when the patient is being weaned off morphine. Coughing on the endotracheal tube and fighting the ventilator complicate the management of patients receiving ventilatory support. Asynchrony between spontaneous ventilatory efforts and mechanical breaths predisposes to pulmonary barotrauma, interferes with alveolar gas exchange, and increases the work of breathing. Neuromuscular paralysis mandates that sedation also must provide amnesia. Benzodiazepines have become very popular sedatives in the ICU over the last decade. Older drugs such as lorazepam and diazepam are long acting and may be difficult to titrate. More recently, midazolam has increasingly replaced these two agents. It is water soluble, short acting, and can be easily titrated in small intravenous boluses or as a continuous infusion. Respiratory or circulatory depression is generally minimal, and even after prolonged infusions its effects usually dissipate within 2 hours after the infusion is stopped. Supplementation of midazolam is important whenever the patient has significant pain, is on a ventilator, or develops tolerance to opioids or other sedatives. Concomitant infusion of an opioid or ketamine augments the sedation, provides analgesia, and reduces total drug requirements. Propofol is also increasingly used for sedation in the ICU as infusions between 15 and 25 /xg/kg/ min. Respiratory and circulatory depression are dose-dependant and generally minimal in this low-

SLEEP DISORDERS IN THE INTENSIVE CARE UNIT Sleep deprivation and insomnia are commonly encountered in modern ICUs. The natural circadian rhythm is altered, causing major disruptions in normal sleep patterns. 16 This can have major implications for both recovery from surgery and the general health of the patient. 17 Sleep deprivation may be caused by internal as well as external factors. Pain, shock, and sepsis are major internal factors. Extemal factors include the noises, bright lights, and alarms that are ubiquitous in the ICU environment and are equally disruptive to normal sleep cycles. Benzodiazepines such as flurazepam, triazolam, and lorazepam are useful at night to help re-establish normal sleep patterns; however, pain must be adequately controlled before the use of these drugs. INTENSIVE CARE UNIT PSYCHOSIS AND PSYCHOSIS-LIKE CONDITIONS Intensive care unit psychosis is a common cause of psychomotor agitation, confusion, restlessness, and even failure to cooperate with deep-breathing exercises and ambulation in postoperative patients. 1s'19 Psychosis can result from increased brain dopaminergic activity that may be caused by illness, drugs, or pain. The psychotic patient cannot understand the nature of his or her illness, environment, or the intent of medical personnel and treatment plans. Primary management of psychosis involves treatment of the underlying cause and immediate control of psychomotor symptoms. Haloperidol, droperidol, or chlorpromazine in small doses are useful in the treatment of this disorder. Extreme agitation initially can be controlled with small doses of midazolam or propofol. However, ICU psychosis must be differentiated from acute depression, which can mimic psychosis. The anticholinergic syndrome also can present symptoms similar to psychosis. An accurate diagnosis is important because the drugs used in the treatment of ICU psychosis can aggravate acute depression or the anticholinergic syndrome.

PAIN RELIEF& SEDATION IN THE ICU DEPRESSIVE ILLNESS IN THE INTENSIVE CARE UNIT Depression is underdiagnosed in ICU patients and often presents as a sleep disorder. The inability of a patient to communicate makes the diagnosis even more difficult. Desiprimine (25 to 50 mg/d) in small doses is very effective in alleviating symptoms. 2o-22

ANTICHOLINERGIC SYNDROME An anticholinergic syndrome can be caused by anticholinergic drugs such as atropine or scopolamine, some opioids, anesthetic agents, antihistamines, antiemetics, and sepsis. 23-26 Restlessness, delirium, confusion, and obtundation characterize this syndrome. It is typically seen in elderly patients. Antipsychotic medications will often worsen the symptoms. Physostigmine can quickly improve symptoms and is useful in making the diagnosis.

85 toms than elderly patients. Benzodiazepine withdrawal appears to be more serious than opioid withdrawal. Careful selection and dosing of sedatives accompanied by a planned, gradual weaning process and the appropriate use of antidepressants and antipsychotic agents can minimize withdrawal symptoms.

CONCLUSION Appreciating and understanding all the patient's problems, maximizing human contact, relieving pain, and ensuring adequate sleep are essential to the care of ICU patients. Altered mental states such depression, psychosis, and the anticholinergic syndrome must be diagnosed and treated appropriately. The emotional needs of the patients should not be neglected in favor of technical expertise. Patients should not be made to suffer indignity, torture, or imprisonment in the ICU at the hands of physicians or ICU personnel. REFERENCES

POSTTRAUMATIC STRESS DISORDER AND ADULT RESPIRATORYDISTRESS SYNDROME Posttraumatic stress disorder is the development of characteristic symptoms after one or more traumatic events. These events involve experiences of intense fear, horror, and helplessness as a result of a stress or threat to one's physical integrity. It has been recently shown that 25% of patients who have suffered from adult respiratory distress syndrome develop posttraumatic stress disorder. 27-31 This may be related to inadequate pain relief and sedation during their management in the ICU.

ACUTE WITHDRAWAL SYNDROMES RELATED TO SEDATIVE MEDICATION IN THE INTENSIVE CARE UNIT Critically ill patients, especially those on ventilators who suffer from the adult respiratory distress syndrome, may require large doses of opioids and benzodiazepines. During weaning from these agents, patients frequently experience withdrawal symptoms. 32-36 A recent study by Cammarano et a136 shows that the frequency of withdrawal symptoms is as high as 32% with opiates and benzodiazepines. Withdrawal symptoms are often observed in mechanically ventilated adults who are in the ICU for more than 7 days. Younger patients and those with the adult respiratory distress syndrome tend to experience more withdrawal symp-

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