Patient controlled analgesia: drug options, infusion schedules, and other considerations

Patient controlled analgesia (PCA) has a number of advantages compared with traditional methods of pain management. Some of these advantages include superior pain relief, less sedation due to superior drug titration, increased psychological satisfaction due to patient control of pain management, individualized analgesic dosing, decreased staff time for patient care, and increased patient activity and mobility. Although a few cases of respiratory depression have been reported with the use of PCA, there is a relatively low risk of this complication in most patient populations. Appropriate candidates for PCA include terminally ill-cancer patients, postoperative patients, mentally clear and alert trauma patients, and patients who require massive doses of oral narcotics to control pain but are experiencing intolerable side effects. This article focuses on the principles involved in selecting the optimal analgesic and the therapeutic variables involved in using PCA.     

Extraordinary analgesic requirement in a patient previously unexposed to narcotics

Patient-controlled analgesia (PCA) is a relatively new therapeutic modality that allows patients to administer doses of intravenous narcotics, using a syringe pump and sequencing device. We used PCA to deliver analgesic therapy to a 35-year-old man seriously injured in an aviation accident. Although the patient gave no previous history of narcotic use or abuse, he required morphine dosing rates as high as 56 mg/h to maintain adequate analgesia. The delivery of relatively high doses of narcotic was not accompanied by significant sedation, as might be expected. The patient underwent two surgical procedures while on PCA therapy. Following each procedure, dosing requirements increased, but within three days after each operation, dosing tapered. The patient was converted to oral hydromorphone therapy, which gradually was tapered and then discontinued. PCA should be considered a useful therapeutic adjunct in the management of patients refractive to empirical narcotic analgesic regimens.     

Efficacy of patient-controlled versus conventional analgesia for postoperative pain

Patient-controlled i.v. administration and intramuscular administration of morphine sulfate were compared in a crossover study to determine their relative effectiveness in relieving postoperative pain. Twenty adult patients scheduled for abdominal surgery were randomly assigned to one of two groups; one group received i.v. morphine sulfate for 24 hours using a patient-controlled analgesia (PCA) device, after which they were given morphine sulfate i.m. for 24 hours. The treatment order was reversed for the other group. Amount of narcotic administered, respiratory rate, and levels of discomfort, activity, and sedation were assessed by the nursing staff every two hours. At the end of each 24-hour treatment phase, patients ranked their level of pain, amount of pain relief, level of sedation, ability to sleep, and ability to perform pulmonary toilet. Patients were also asked whether they preferred PCA or i.m. analgesic therapy for future surgery. Patients reported significantly less discomfort while using PCA than during i.m. morphine administration. No significant differences in amount of narcotic used, respiratory rate, nausea and vomiting, or levels of activity or sedation were noted for the two regimens. Patients' rankings of the two treatment modes did not differ significantly, but a majority of patients indicated a preference for future use of PCA. In these postoperative patients, administration of i.v. morphine sulfate by PCA was as safe as i.m. administration and possibly more effective in relieving pain.     

Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient-controlled analgesia

In postoperative patients using patient-controlled analgesia (PCA) to administer i.v. doses of morphine sulfate, respiratory rates and subjective rankings of pain, sedation, and liking for the drug were correlated with plasma morphine concentrations. In 12 patients selected before surgery, the initial morphine sulfate dose of 0.6 mg/sq m was increased or decreased as needed. Every two hours, cumulative morphine sulfate dose, respiratory rate, and sedation were recorded by the nurse, along with the patient's evaluation of pain and liking for the drug. Plasma was collected in the morning and evening during PCA therapy for morphine analysis. Data were analyzed by analysis of covariance. Dosing rates and rankings of pain, sedation, and liking decreased as a function of time postoperatively, but respiratory rates did not. Sedation and respiratory rates were independent of morphine concentration. Liking of the drug increased directly with plasma morphine concentration but decreased with time. A high level of pain was directly related to morphine use. For all significant relationships, there was high interpatient variability, with the exception of changes in pain rankings induced by morphine. Patients defined a minimum effective plasma morphine concentration of 20-40 ng/mL. The maximum plasma morphine concentration achieved by self-administration was 82 ng/mL. These postoperative patients used patient-controlled analgesia to deliver morphine sulfate i.v. for pain relief, not for euphoria, and did not exhibit sedation or respiratory depression. Morphine was consistently effective at plasma concentrations of 40 ng/mL or greater.     

Continuous nasogastric morphine infusion

Morphine sulfate is the narcotic analgesic most commonly used for pain treatment in terminally ill patients. This case report demonstrates a new method of morphine administration. A 56-year-old terminally ill cancer patient with severe pain from metastatic adenocarcinoma of the lung required continuous nasogastric feeding and around-the-clock narcotic analgesics. The patient was safely and effectively converted from a continuous intravenous morphine infusion to continuous nasogastric morphine-enteral feedings. This method of administration may benefit patients receiving continuous enteral tube feedings who either require high-dose morphine therapy or are unable to use the oral administration route.     

Analgesia with oral narcotics and added ibuprofen in cancer patients

A scheduled regimen of oral narcotic analgesics was compared with a regimen of oral narcotic analgesics plus ibuprofen for analgesic efficacy in patients with cancer. Ten patients with metastatic cancer were randomly assigned to receive either ibuprofen 400 mg or a look-alike placebo four times daily in addition to each patient's existing regimen of scheduled oral narcotics. A two-period changeover study design was used. The 24-hour narcotic intake equated to injectable morphine was computed for each patient at baseline and during the nine study days. A visual analogue scale was used to evaluate pain relief, nausea, mood depression, daytime drowsiness and nighttime sleeplessness. The analgesic efficacy of the narcotic-ibuprofen combination was significantly greater than the analgesic efficacy of the narcotic-placebo combination. Eight patients demonstrated a positive treatment effect with added ibuprofen; the overall improvement in analgesia averaged 39.1% in these patients. There was no significant increase from baseline in the incidence of nausea, mood depression, daytime drowsiness or nighttime sleeplessness. At the doses used in this study, a treatment regimen of oral narcotic analgesics plus ibuprofen was more effective than oral narcotics alone in relieving pain associated with cancer.     

Patient-controlled analgesia: a review.

The patient-activated analgesic system was introduced in 1968. Early trials, although uncontrolled, supported the safety and efficacy of patient-controlled analgesia (PCA) in several kinds of pain, such as that relating to surgery, cancer, trauma, and obstetric procedures. In the past decade, prospective, randomized trials have reported several advantages of PCA over conventional analgesia in the early postoperative period. Although not supported by all controlled trials, they include improved pain relief, less sedation, lower level of narcotic consumption, fewer postoperative complications, greater patient satisfaction, and improved pulmonary function. Preliminary results in the management of chronic pain indicate that PCA can lead to significant lifestyle improvements in ambulatory patients with cancer. The most significant, although infrequent, adverse effect is respiratory depression, the majority of cases occurring in patients predisposed secondary to concomitant illness or as a result of human error. The clinical use of PCA will likely see a significant increase among persons with cancer, and an increase in epidural administration. The cost benefit of PCA has yet to be assessed in inpatient and outpatient settings.     

Postoperative patient-controlled analgesia in the elderly: risks and benefits of epidural versus intravenous administration

Postoperative patient-controlled analgesia provided by the intravenous route using morphine (PCA) or by the epidural route using an opioid in combination with a local anaesthetic (patient-controlled epidural analgesia; PCEA) is not yet routinely used in the elderly. However, this modality theoretically provides adequate control of postoperative pain in such patients. Firstly, an assessment of the level of pain is particularly difficult in the elderly, and patient-controlled techniques that enable the self-administration of analgesic could resolve this problem. Secondly, these techniques provide a fine and controlled titration of analgesic doses. Since analgesic-induced adverse effects increase with age, the risk of overdose is therefore reduced. Thirdly, effective postoperative patient-controlled analgesia may attenuate detrimental physiologic responses, and contribute to improvement in patient outcomes. In the elderly, PCEA provides better pain relief, particularly for dynamic pain, and improves postoperative recovery with a low incidence of adverse effects compared with PCA. PCA and PCEA techniques have a good safety profile in the elderly only when there is careful preoperative patient selection and strict postoperative monitoring. Standard observation of vital signs, sedation and pain scores and assessment of mental status are required. Patient selection is necessary to identify those patients who may be incapable of using the device (e.g. patients with evidence of cognitive dysfunction or physical disabilities). In addition, caution is required among patients with respiratory, renal or hepatic insufficiency. PCA and PCEA are particularly useful for elderly patients undergoing major thoraco-abdominal surgery. However, there is a need for further research in elderly patients. In the future, improvements in the management of postoperative pain in the elderly will lead to a greater expansion of self-controlled techniques.     

患者自控镇痛泵用于口腔颌面部外科术后的效果观察

目的獉獉:探讨患者自控镇痛泵(PCA)在口腔颌面外科手术后镇痛的作用。方法獉獉:94例口腔颌面外科手术后患者随机分为两组,分别给予PCA和传统镇痛方法,采用VRS评分法比较自控镇痛泵与传统镇痛方法对病人止痛镇静的效果。结果獉獉:与传统方法相比,PCA对病人的止痛镇静效果更好。结论獉獉:患者自控镇痛泵静脉给药能够减轻甚至消除疼痛,提高了口腔颌面部手术后患者的生活质量。     

胸科手术后舒芬太尼静脉镇痛的剂量探讨

目的探讨普胸外科术后舒芬太尼静脉镇痛的合理剂量和效果。方法120例普胸外科术后患者随机分为4组（每组30例），A组（芬太尼30μg／h＋PCA7．5μg/次，锁定时间15min），B组（舒芬太尼3μg／h＋PCA0．5μg／次，锁定时间10min），C组（舒芬太尼4μg／h＋PCA 0．5μg／次，锁定时间15min），D组（舒芬太尼5μg／h＋PCA0．5μg／次，锁定时间30min），记录术后4、8、16、24、48h的疼痛、镇静、情绪及睡眠质量评分，并记录有无恶心、呕吐、呼吸抑制、皮肤搔痒等不良反应，记录镇痛泵输注情况、实际及有效按压次数，计算单位时间用药量。结果4组间镇静、情绪、睡眠质量评分以及不良反应差异无统计学意义（P〉0．05），D组疼痛评分显著低于其他3组（P〈0．05）；PCA泵按压次数最少，B、C、D组单位时间实际用药量大致相近。结论普胸外科术后舒芬太尼静脉镇痛的最佳剂量为5μg／h，且恒速输注比反复追加给药更容易为患者所接受。     

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.     

Epidural analgesia.

The process of nociception, the anatomy of the epidural space, and the placement of the epidural catheter are reviewed, and the pharmacology and pharmacokinetics, analgesic efficacy, and potential adverse effects of epidurally administered narcotics and local anesthetics are discussed, as well as patient monitoring standards and solution preparation guidelines for these agents. The epidural space is located between the dura mater (the outer-most membrane surrounding the spinal cord) and the vertebral canal. The site of catheter placement is determined by the dermatomes corresponding to the site of desired analgesia. The primary factors that differentiate epidural narcotics are related to their pharmacokinetic profiles. Morphine, which is hydrophilic, has a slower onset of action and a longer duration of analgesia than lipophilic compounds such as fentanyl; morphine also results in less segmentalization (the degree to which analgesia is limited to discrete dermatomal segments corresponding to the level of the epidural narcotic injection) than is seen with lipophilic compounds. Studies have shown that epidural narcotics provide superior pain relief compared with systemic narcotics. Common adverse effects associated with therapeutic doses of intraspinal narcotics include itching, nausea and vomiting, urinary retention, and sedation; respiratory depression is uncommon after epidural administration of narcotics. The most bothersome adverse effect encountered with analgesic doses of local anesthetics is paresthesia. Solutions for epidural administration must be sterile and preservative free. Epidural administration of narcotics and local anesthetics seems to provide better pain relief than conventional methods but may be associated with more bothersome adverse effects.     

Sedation and analgesia in critically ill neurologic patients

Critically ill neurologic patients can pose a challenge when it comes to providing sedation and analgesia, primarily with the balance of maintaining sedation to provide patient comfort while still allowing a neurological examination. Determination of the optimal agent requires assessment and understanding of the underlying requirement for sedation: provision of analgesia, anxiolysis, or treatment of delirium. Pharmacological options exist that can affect individual or multiple underlying sedation requirements. Numerous evaluation tools exist to monitor the efficacy of sedation as well as help clinicians titrate agents to predefined goals; these tools allow the safe administration of drugs that can otherwise have serious adverse effects. Sedation regimens must ultimately be individualized to each patient to account for differences in pharmacokinetics and dynamics of the various agents, and this is particularly true in sedating neurologically injured patients. The agents frequently used to provide sedation and analgesia in the critically ill neurologic patient will be reviewed.     

The use of sedative agents in critically ill patients.

The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.     

Patient-controlled analgesia in the management of postoperative pain

Patient-controlled analgesia (PCA) is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain. Since its introduction in the early 1980s, the daily management of postoperative pain has been extensively optimised. The use of PCA in hospitals has been increasing because of its proven advantages over conventional intramuscular injections. These include improved pain relief, greater patient satisfaction, less sedation and fewer postoperative complications. All PCA modes contain the following variables: initial loading dose, demand dose, lockout interval, background infusion rate and 1-hour or 4-hour limits. Morphine is the most studied and most commonly used intravenous drug for PCA. In spite of the fact that it is the 'first choice' for PCA, other opioids have been successfully used for this option. The most observed adverse effects of opioid-based PCA are nausea and vomiting, pruritis, respiratory depression, sedation, confusion and urinary retention. Although intravenous PCA is the most studied route of PCA, alternative routes have extensively been described in the literature. PCA by means of peridural catheters and peripheral nerve catheters are the most studied. Recently, transdermal PCA has been described. The use of peripheral or neuraxial nerve blocks is recommended to avoid the so called opioid tolerance observed with the intravenous administration of opioids. Numerous studies have shown the superiority of epidural PCA to intravenous PCA. The beneficial postoperative effects of epidural analgesia are more apparent for high-risk patients or those undergoing higher risk procedures. PCA with peripheral nerve catheters results in increased postoperative analgesia and satisfaction for surgery on upper and lower extremities. Serious complications occur rarely with these catheters. With the introduction of an Acute Pain Service, management of postoperative pain can be improved. This will also help to minimise adverse effects related to PCA and to avoid lethal mishaps.     

Comparison of the analgesic effect of patient‐controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery

Oxycodone is a μ‐opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient‐controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient‐controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%–75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4–83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4–103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient‐controlled oxycodone provides similar effects for pain relief compared to patient‐controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery.     

Emergency department management of pain and anxiety related to orthopedic fracture care: a guide to analgesic techniques and procedural sedation in children

Orthopedic fractures and joint dislocations are among the most painful pediatric emergencies. Safe and effective management of fracture-related pain and anxiety in the emergency department reduces patient distress during initial evaluation and often allows definitive management of the fracture. No consensus exists on which pharmacologic regimens for procedural sedation/analgesia are safest and most effective. For some children, control of fracture pain is the primary goal, whereas for others, relief from anxiety is an additionally important objective. Furthermore, strategies for the management of fracture pain may vary by fracture location and patient characteristics; thus, no single regimen is likely to provide the best means of analgesia and anxiolysis for all patients. Effective analgesia can be provided by local or regional anesthesia, such as hematoma, Bier, or nerve blocks. Alternatively, induction of deep sedation with analgesic agents such as ketamine or fentanyl, often combined with sedative-anxiolytic agents such as midazolam, may be used to manage distress associated with fracture reduction. A combination of local anesthesia with moderate sedation, for example nitrous oxide, is another attractive option.     

目标不等于目的——浅谈镇痛镇静的器官保护作用

镇痛镇静治疗的目的在于保护器官的形态与功能储备。在能够满足全身各组织器官代谢最低需求的循环灌注与氧合的基础上,让器官尽量休息且功能和谐匹配,以最大限度地节约和保护器官的储备功能,使得危重患者康复后能够尽可能保持较好的生活质量,是重症医学可持续发展的重要基础。在达到镇痛镇静治疗目的的过程中,需要根据患者的病情、基础状态、器官功能等个体化设置不同的镇痛镇静目标,而不宜简单机械地强调“深镇静”或“浅镇静”。镇痛镇静治疗是一把双刃剑,无监测,勿镇痛镇静;实施镇痛镇静治疗时需要对治疗是否已顺序达到镇痛镇静目标,并趋近器官功能保护目的进行连续的监测与评估,但此监测与评估不能仅局限于对患者疼痛和意识及认知状态的了解,还必须包括对患者基本生命体征的动态变化以及器官功能的储备代偿能力判断,运用监测评估的手段,使机体各器官达到休整生息、尽量多保留储备功能、减少慢重症、提高生活质量之目的。     

Hospital pharmacy-based service for patient-controlled analgesia

A hospital pharmacy-based patient-controlled analgesia (PCA) service is described. The pharmacy department at a 255-bed community hospital instituted a comprehensive PCA service in 1985. Pharmacists were given thorough training in the clinical aspects of pain management and were taught how to use the PCA device; nurses also received instruction. An order for PCA is issued by a physician, who may then delegate decisions about medication choice, duration of therapy, and device settings to a clinical pharmacist. The pharmacist reviews the order and evaluates the patient's status. If PCA is appropriate, the pharmacist selects the analgesic agent and PCA device settings and prepares a pharmacy monitoring card. Orders for syringes are filled in the central pharmacy or by the decentralized pharmacist. Each order is entered into the i.v. drug profile and the i.v. drug computer file, and a narcotics control card is completed. The nurse programs the device, instructs the patient, and records the patient's level of pain control on a PCA-monitoring record. The pharmacist observes patients daily and records observations and changes on the pharmacy monitoring card. Use of the PCA service has grown from an average of 56 patient days per month in 1985 to 919 in 1989, and pharmacy department revenue has increased accordingly. A moderate increase in workload has been absorbed without the need for an increase in staff. Surveys show broad acceptance of the service by physicians, nurses, and patients. A hospital pharmacy-based PCA service offered patients better control of pain, allowed pharmacists to demonstrate competence in non-distributive functions, increased the visibility of the pharmacy department, and was a source of revenue.     

A computer-based system for controlling plasma opioid concentration according to patient need for analgesia

Microprocessor-controlled infusion pumps, which allow a patient to self-administer bolus doses of an analgesic to relieve pain, are becoming commonplace. While these patient-controlled analgesia (PCA) systems overcome the large interpatient variations in pharmacokinetics, they do not provide steady relief from pain since they rely on delivering a drug in small, incremental doses. To overcome this problem, the authors developed an algorithm and computer-pump system that allows patients to control their own plasma concentration of analgesic. This approach uses individually predetermined pharmacokinetic parameters to provide steady plasma opioid concentrations that can be increased or decreased by the patient in line with the need for more pain relief or fewer side effects. The control software uses a novel, recursive algorithm to compute the pump rates necessary to maintain constant plasma drug (e.g. morphine) concentrations at desired values and to reach a new steady concentration in response to patient requests. This report describes the mathematical approach to the problem of control of plasma opioid concentration, the application of this new drug delivery system to management of persistent pain in cancer patients undergoing bone marrow transplantation, and the magnitude of pharmacokinetic variability with morphine in this patient population. Results are presented from individual patients using this adjustable drug delivery system continuously for up to 2 weeks to control pain from oral mucositis.