Pain can be defined as an unpleasant sensory and emotional experience associated with actual or potential damage to tissues; and analgesia therefore means the absence of pain in the presence of noxious stimulation .
The critically ill patient suffers pain not only due to the underlying disease (e.g. multiple trauma, extensive surgical interventions due to abdominal septic states, etc.); but also due to diagnostic or therapeutic interventions. The adequate treatment of pain in ICU patients must be an integral part of the ICU measures, as inadequately treated pain leads to a series of complications (Table 1), that themselves may counteract the treatment and will have an adverse influence on the outcome of the critically ill .
A number of factors influence the intensity, quality and duration of pain in the post-traumatic and postoperative patient. These include the site, nature and duration of surgical intervention; the type and the extent of the incision and other surgical trauma; the physiological and psychological make-up of the patient; the psychological and pharmacological preparation of the patient; the presence of complications related to the surgical intervention; and the anaesthetic management.
Systemic application of analgesic drugs
Continuous intravenous administration
Continuous intravenous administration of analgesics is widely used in mechanically ventilated critically ill patients. This produces an even level of analgesia, avoiding peaks and valleys of the concentration of the substance used. The continuous infusion rate can be supplemented by boluses of the analgesic drug if needed for therapeutic or diagnostic procedures.
Sufentanil, a derivate of fentanyl which is about 10 times more potent, is widely used in the critically ill. It is a highly selective μ-agonist and combines two effects that are both desirable in ICU-patients: analgesia and sedation. In mechanically ventilated patients sufentanil is recommended in a dose of 0.75-1.0 μg kg−1 h−1. Most of the patients treated are calm but cooperative (Ramsey score 2: cooperative or tranquil; 3: response to commands only) and do not suffer pain. When starting a sufentanil infusion it may be necessary to add a bolus of about 50-100 μg to achieve rapid analgesia and to avoid the patient reacting against the ventilator. For diagnostic or therapeutic procedures it may be necessary to add an additional bolus of sufentanil (25-50 μg). If necessary, additional sedation is achieved with a benzodiazepine such as midazolam .
A continous infusion of sufentanil can also be used in intubated and spontaneously breathing patients while they are being weaned from the ventilator. For this it is necessary to decrease the infusion rate to about 0.25-0.35 μg kg−1 h−1. Within 2 hours, the patient is able to breathe spontaneously without the danger of respiratory depression. As the plasma level of sufentanil decreases rapidly after reducing the dose, this regime can also be used in non-intubated critically ill patients .
Patient-controlled analgesia (PCA)
If the critically ill patient is well co-ordinated, intubated and breathing spontaneously with an assist device, or if the patient is extubated, on-demand analgesia may be an alternative to a relatively fixed continuous infusion of an analgesic drug. PCA can be given via the intravenous or the epidural route. To be successful, however, it is necessary for both the patient and the nurses to understand the basic concept of PCA. This means that the patient should be given an explanation of the PCA device and should be encouraged to use it prophylactically to pre-empt discomfort .
The major advantages of PCA compared to conventional techniques are the high quality of analgesia, autonomy, elimination of the delay between the decision to treat and its actual treatment, and freedom from painful intramuscular injections.
The properties of an ideal analgesic agent used in PCA are: rapid onset of analgesic effect, highly efficacious in relieving pain, intermediate duration of action to improve controllability, no production of tolerance or dependence and no side effects or adverse drug interactions .
A large number of analgesic drugs can be used in PCA. Therapeutic guidelines for the commonly used drugs are summarized in Table 2. Whether an additional continuous basal infusion of the analgesic offers advantages for the patient is still in debate, although many workers believe that any benefit is bought at the price of safety. In our opinion a continuous basal infusion of the drug should be administered to guarantee an optimal analgesic effect especially during sleep. This infusion should be tailored to the requirements, which means that the basal rate should be decreased to about the half of the initial one when the peak of post-traumatic or postoperative pain is past [6,7].
PCA is, however, not free of risks; large bolus doses or short lock-out intervals can lead to respiratory depression. Adjustments of the bolus dose or the basal infusion rate are necessary in order to optimize the therapy and to prevent untoward side effects. This means that a pain service has to be installed. During long-lasting continuous administration of narcotics tolerance will develop to both the desirable and undesirable effects: progressively larger doses will be required to achieve the same degree of pain relief and, when opioids are discontinued, withdrawal symptoms can be experienced as a result of physical dependence . Further possible complications are listed in Table 3.
Transdermal drug application
In some ICU patients, especially those who are recovering from a serious illness but still need analgesia, the transdermal application of opioid drugs is an alternative to continuous drug infusion or PCA. Advantages of this kind of opioid application include decreased gastrointestinal degradation and less first-pass hepatic metabolism, stable plasma concentrations, improved patient compliance through extreme ease of administration, dose intervals longer than 1-2 days, and decreased risk of infection. The major disadvantages of transdermal administration are the inability of the system to respond rapidly to changing requirements, a fivefold variability in analgesic requirements between patients, and the slow onset of analgesia. Increased analgesic requirements can be accomodated by increasing the size of the patch (25, 50, 75, 100 cm2), which provides sustained transdermal rates of approximately 25, 50, 75 and 100 μg h−1 fentanyl over a period up to about 72 hours. The underlying concept is to mimic a continuous intravenous infusion; the future will show whether this concept will also be a useful method for the treatment of ICU patients [5,8,9].
Regional application of analgesic drugs
Under some circumstances, especially in patients with trauma of the thorax, pelvic fractures, or after major surgery involving the thorax or the abdomen, regional analgesia, alone or in combination with systemic analgesia, is an alternative technique to continuous intravenous medication [9-13].
There are several advantages of epidural drug administration over the intravenous route. Pain relief is superior at a smaller cumulative dose compared with other methods, although supplementary opioid administration for relief of additional pain during therapeutic or diagnostic manipulation and stress is sometimes necessary; there is less sedation and respiratory depression; a mixture of local anaesthetics with opioids appear to be more efficacious than the continuous application of a single agent; epidurally administered local anaesthetics cause a sympathetic block, which may reduce the incidence of deep vein thrombosis and pulmonary embolism in patients at risk. Important advantages of continuous epidural infusion are a decrease in the overall mortality and morbidity, a reduction in the post-traumatic and postoperative complication rate, a shorter stay in the ICU and a shorter overall duration of hospitalization. The effect on the post-traumatic stress response is more controversial.
A wide spectrum of drugs has been administered epidurally, including narcotics, local anaesthetics and α-adrenergic agonists (e.g. clonidine). The advantages of the newer opioids (fentanyl, alfentanil, sufentanil) over morphine are their higher lipid solubility, which results in a more rapid onset of action, fewer adverse effects and a reduced risk of late respiratory depression. From the spectrum of local anaesthetics, bupivacaine has gained wide popularity due to its long duration of action. The combination of a local anaesthetic with an opioid is an excellent choice for pain relief because these drug groups have different mechanisms of action and therefore lower concentrations of each drug can be used in combination than when either agent is used alone [14-16].
Table 4 gives guidelines for continuous epidural administration of local anaesthetics and opioids. It is important to notice that drugs applied epidurally should be free of neurotoxic preservatives such as methylparaben or benzyl alcohol.
Offsetting the advantages, one must recognize extra complications that can result from complications of the catheter placement or from adverse drug reactions. Complications associated with catheter placement can be an inadvertent dural puncture, infection or bleeding into the epidural space, catheter migration after placement and inappropriate injection of drugs through the epidural catheter. Among the adverse drug reactions, respiratory depression is the most feared. Several factors may contribute to this complications, e.g. additional supplementation with intramuscular or intravenous opioids during epidural analgesia. Careful monitoring of the patient (pulse oximeter, end-tidal carbon dioxide monitor) is essential. A less serious adverse reaction of epidural opioids is pruritus; other undesirable effects of epidurally administered narcotics are urinary retention, nausea and vomiting, neurologic effects, tachyphylaxis and, in rare cases, systemic toxicity. Sedation may also accompany epidural opioids, but to a lesser degree than with systemic use (Table 5).
Contraindications to epidural analgesia include inexperience with performing an epidural block, known opioid allergies, especially in septic patients, infection at the site of insertion, and bleeding complications.
To achieve optimal results, pain treatment in the critically ill patient should follow a step-by-step approach: during the initial phase of ICU care the patient will need optimal analgesia combined with adequate sedation; this goal can best be reached using continuous intravenous administration of drugs, titrated to the patient's needs. In our experience, continuous intravenous sufentanil is the drug of choice. Under special conditions, simultaneous application of analgesic drugs via the epidural route may facilitate the handling of the patient, reduce the total amount of drugs given, minimize the complications due to the different methods used and achieve better pain relief than can be achieved by the administration of an analgesic drug by continuous intravenous infusion.
Later during the ICU stay, when the critically ill patient has better co-ordination, the use of PCA should be kept in mind; PCA can be managed using intravenous or epidural administration of analgesic drugs.
During the final period in the ICU-the rehabilitation phase-pain can also be treated using the transdermal route.
To achieve the best results for the criticall ill using different techniques for pain relief it is necessary to be well informed and trained with the method, to know the advantages and disavantages, the correct and appropriate dose of the drugs to be used and the indications and contraindications.
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Seventh International Symposium on Intravenous Anaesthesia, Lausanne, Switzerland, 2-3 May 1997
This publication is supported by grants from various pharmaceutical companies. The views in this publication are those of the authors and not necessarily those of supporting companies. Drugs and administration techniques referred to should only be used as recommended in the manufacturers' prescribing information.