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We continue our discussion of the most commonly used analgesics in the management of pain, opioids. Today we consider addiction.

A 58 year-old man with an infected total knee replacement is recovering from an incision and drainage procedure. He has been in the hospital for 5 days and has been receiving intravenous morphine via a Patient Controlled Analgesia (PCA) device for his pain. The patient has been taking aspirin as his only analgesic for the last 5 years. The patient complains to you that his dose of morphine, which was previously adequate, is now not enough. This is the 3rd time in the last 3 days that this patient has reported this.
1.  What is the difference between tolerance, addiction, and physical dependence?
2.  Has this patient become addicted?
3.  How often do patients become addicted to opioids as hospital in-patients?
58岁男性，全膝关节置换术后感染，给予切开引流处理。入院5天，一直静脉给予吗啡PCA镇痛治疗。患者过去5年中一直靠服用阿司匹林缓解疼痛，患者抱怨说在以前有效的吗啡现在效果不好，这已经是过去3天以来病人第三次诉说这种情况了。

1．耐药性、成瘾性与身体依赖的区别是什么？
2．该患者属于成瘾吗？
3．医院内患者对阿片药物成瘾的可能性有多大？

[每周一问]NO.3之周中问参考答案

耐药性、成瘾性与身体依赖的区别是什么？

耐药性指需要增加药物剂量才能发挥相同的治疗效果。
成瘾性指机体的一种强迫性行为反应状态，通常包括连续或规律的服药以体验其精神作用和/或避免因药物缺乏导致的不适感。
身体性依赖是指当药物在应用一段时间后停止服用时机体出现以停药综合征为特征的一种生理状态，对阿片类药物来说，其代表特征为焦虑、易激、寒战、出汗、恶心、呕吐和失眠等。身体依赖不同于成瘾，在长期应用阿片药物的患者停药时可以预测到。

该患者属于成瘾吗？

对于上述这个需要增加吗啡剂量的患者，判断患者是否是由于下肢感染加重而导致疼痛加重非常重要。需要增加阿片药物的一个很普遍的原因就是导致疼痛的疾病病情加重；除此之外，最常见的原因是药物的急性耐受。对于那些长时间持续疼痛的患者应用阿片药物可以发生急性耐药性。在手术后病人很少出现急性耐药性，因为疼痛程度因为伤口的愈合很快降低。动物研究表明，对阿芬太尼数小时即可出现急性耐药。对志愿者使用雷米芬太尼发现，对于疼痛刺激持续静脉输注3小时后出现急性耐受。

医院里患者对阿片药物成瘾的可能性有多大？

手术后患者出现成瘾很罕见。可惜遗憾的是，对成瘾的恐惧经常导致没有理由的阿片类药物剂量减少。在一项12000名接受阿片止痛的住院病人研究发现，只有4名患者被认为成瘾。对成瘾的恐惧不能成为降低术后阿片药物剂量的合理理由。

对耐药性的治疗是当患者需要增加时增加药物剂量。通常，对吗啡副作用的耐受比对其镇痛作用发生更迅速。

[每周一问]NO.3之周中问英文版

What is the difference between tolerance, addiction, and physical dependence?

Tolerance refers to the need for increasing doses of a drug to produce the same effect.
Addiction refers to a state characterized by behavioral responses that always include a compulsion to take the drug on a continuous or regular basis in order to experience its psychic effects and/or to avoid the discomfort of its absence. This continued use occurs despite adverse social, physical, psychological and emotional consequences. Tolerance may or may not be present.
Physical Dependence is a physiological state characterized by a set of withdrawal symptoms when the drug is withheld after a period of administration. For opioids, it may be characterized by anxiety, irritability, chills, diaphoresis, nausea, vomiting and insomnia. Physical dependence is not the same as addiction and is a predictable outcome with termination of long-term opioid use.

Has this patient become addicted?
With the above-described patient who has escalating needs for morphine, it is important to verify that the cause is not due to worsening of the patient’s underlying infection. A very common cause for the increasing opioid demand is progression of the pain-causing disease process. With that excluded, the most common cause of increasing dosage requirements is acute tolerance. Acute tolerance can occur rapidly with opioids in patients who have a constant degree of pain over many days. This is not commonly seen postoperatively because the degree of pain is rapidly declining as the wound heals. Animal studies have revealed acute tolerance to alfentanil occurring over a matter of hours. Human volunteer studies using remifentanil have shown that acute tolerance with regard to painful stimuli occurs as quickly as three hours with continuous iv infusions (2).

How often do patients become addicted to opioids as hospital in-patients?
Addiction in postoperative patients is extremely rare and unlikely. Fear of addiction is an unfounded, but unfortunately, common reason for underdosing of opioids. In a study of 12,000 in-house patients receiving opioids for pain, only 4 patients were considered to be possibly addicted (3). Fear of addiction is not a justifiable reason to withhold adequate opioid analgesia postoperatively.
The treatment for tolerance is to increase the dose as the patient’s requirements increase. In general, tolerance to the adverse effects of morphine occurs more rapidly than to its analgesic effects.
References:
1.  Max MB, Payne R, Edwards WT, Sunshine A, and Inturrisi CE. Principles of analgesic use in the treatment of acute pain and cancer pain, 4th edition. American Pain Society, 1999.
2.  Vinik HR and Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg 1998; 86:1307-11.
3.  Porter J and Jick J. Addiction rare in patients treated with narcotics. New Engl J Med 1980; 302:123-6.
4.  Bruera E, Macmillan K, Hanson J, MacDonald RN. The cognitive effects of the administration of narcotic analgesics in patients with effects of the administration of narcotic analgesics in patients with cancer pain. Pain 1989; 39:12-16.
5.  Hill SC. Painful prescriptions. JAMA 1987; 257:2081-2.