Cancer Pain Management: Opioids

Opioids are the most effective analgesics for cancer pain treatments. But the ineffective treatment of cancer pain is often related to insufficient knowledge of opioids and fear of the addiction along with the side effects. To achieve effective treatment of cancer pain with opioids, we need a careful assessment of pain, proper use of opioids and regular review of the effectiveness of prescribed opioids. Basic principles of opioids therapy in cancer pain are 1. Oral opioids (or transdermal) if possible; 2. Combination of long-acting opioids for constant pain with short-acting opioids for breakthrough pain; 3. "Opioids rotation"in poor analgesia and significant side effects with the calculations of the morphine equivalent daily dose (MEDD) 4. Initiation of prophylactic treatment for constipation and nausea. In this review, I will describe the essential aspects of opioids therapy, pharmacology, rotation, properties of the individual opioids, and management of common side effects.

A case involing anesthesia for middle cerebral artery-distal internal carotid artery bypass surgery for a ruptured cerebral aneurysm in a patient with a descending aortic dissection and who had previously undergone a bentall operation: A case report

We experienced a case of middle cerebral artery-distal internal carotid artery bypass surgery for treating a ruptured cerebral aneurysm in a 50-year-old female who also had a descending aortic dissection and a past history of receiving a Bentall operation for an ascending aortic dissection 7 years previously. The patient successfully underwent surgery and we report on this experience along with a brief review of the relevant literature.

Incision-induced Pain Behaviors in the DBA/2 Mouse / 대한통증학회지

BACKGROUND: Because genetic manipulation is commonly accomplished in mice, mouse models for pain have advanced our understanding of the mechanisms of persistent pain. The purpose of this experimental study is to develop a mouse model for understanding incision induced postoperative pain. METHODS: A longitudinal incision was made at the hindpaw of male DBA/2 mice. The withdrawal frequency (WF) from applications of von Frey filaments and the response frequency (RF) to blunt mechanical stimulation were examined in an incision group and a control group. The withdrawal latency (WL) to radiant heat and a pain score based on weight bearing were also measured. Tests were performed 1 day before incision, and 2 hours, 1.3 days, 5 days and 7 days after incision. RESULTS: The WF for the strongest filament was 35.0 +/- 9.1% before incision and this increased to 100.0 +/- 0% at 2 hours and to 65.0 +/- 9.1% at 7 days after incision. The RF to the blunt stimulus was 4.1 +/- 4.1% before incision and 100.0 +/- 0.0% at 2 hours and 42.8 +/- 10.8% at 7 days after incision. The WL was 6.6 +/- 0.5 sec before incision and 2.4 +/- 0.3 sec at 2 hours and 5.9 +/- 0.6 sec at 7 days after incision. The pain score increased from 1.1 +/- 0.8 to 7.4 +/- 1.5 at 2 days after incision. CONCLUSIONS: A mouse model of acute postoperative pain was developing by making a surgical incision in the mouse hindpaw. Mechanical hyperalgesia and allodynia lasting for several days demonstrate that this model has similarities to the human post-operative pain state. Future studies will allow us to further investigate the genetic and molecular mechanisms of incisional pain.

Comparison of Changes in Arterial Blood Gases during Endoscopic Thyroidectomy, Laparoscopic Cholecystectomy and Gynecologic Laparoscopic Surgery / 대한마취과학회지

BACKGROUND: Because laparoscopic surgery has many advantages compared with conventional methods, it has recently been applied to not only intraabdominal or intrathoracic surgery but also thyroidectomy. It is possible that arterial blood gases and hemodynamic variables can be changed by patient position and insufflation of pressurized CO2 into extraperitoneal or intraperitoneal space, so we examined the changes in arterial blood gases, end tidal CO2 (P(ET)CO2) and hemodynamic variables during an endoscopic thyroidectomy with extraperitoneal CO2 insufflation, laparoscopic cholecystectomy and gynecologic laparoscopic surgery with intraperitoneal CO2 insufflation under N2O, enflurane inhalational general anesthesia. METHODS: Forty ASA class I or II patients were included in this study, endoscopic thyroidectomy group (n = 10), laparoscopic cholecystectomy group (n = 18), gynecologic laparoscopic surgery group (n = 12). All patients were underwent controlled mechanical ventilation (tidal volume: 10 ml/kg, respiratory rate: 12/min) and the ventilator mode was fixed in this volume and rate until the end of the operation. The position of patients during the endoscopic thyroidectomy and laparoscopic cholecystectomy were under 5 degree reverse Trendelenburg position, whereas the gynecologic laparoscopic surgery was under a 10 degree head-down lithotomy position. Variables were measured before CO2 insufflation (10 minute after induction), 10, 20 and 30 minutes after CO2 insufflation and 40 minutes after CO2 deflation. RESULTS: PaCO2 and P(ET)CO2 were significantly increased during CO2 insufflation compared with preinsufflation values in all groups, but the magnitude of increases of PaCO2 and PETCO2 was not significantly different among the three groups. The mean magnitude of increases of PaCO2 at 10 minutes after CO2 insufflation were as follows: gynecologic laparoscopic surgery (6.21 +/- 2.0 mmHg), endoscopic thyroidectomy (5.07 +/ 2.3 mmHg), and laparoscopic cholecystectomy (5.01 +/- 2.2 mmHg). CONCLUSIONS: We concluded that PaCO2 and P(ET)CO2 were significantly increased during CO2 insufflation compared with the preinsufflation values in all groups, but the magnitude of increases of PaCO2 and P(ET)CO2 was not significantly influenced by CO2 insufflation site and patient position.

Unilateral Cervical Sympathectomy Attenuates Hypertensive Responses Induced by Intracerebroventricular Administration of Choline in Rats / 대한마취과학회지

BACKGROUND: Brain acetylcholine is an important neurotransmitter in the control of blood pressure. Pharmacological activation of central cholinergic receptors by intracerebroventricular (ICV) administration of choline resulted in a marked pressure response in hypotensive experimental models, and the pressure response was associated with an increase in plasma vasopressin levels. The aim of this study was to determine whether a unilateral cervical sympathectomy affects the pressure response induced by ICV choline. METHODS: Rats were prepared with a cervical sympathectomy or with a sham operation and a 23 G cannula was implanted into the lateral cerebral ventricle. They were divided into three groups according to the pre-treated condition and the solution injected into the lateral cerebral ventricle; group 1 (ICV saline after sham operation), group 2 (ICV choline after sham operation), group 3 (ICV choline after cervical sympathectomy). Following the recovery period, pressure response was monitored for 50 min after injecting ICV choline or saline and plasma vasopressin levels were also assessed with an EIA kit at preinjection time, 10 min, and 50 min after ICV injection. RESULTS: The baseline systolic blood pressure was 120.6 +/- 3.9 mmHg in group 3 and 121.7 +/- 9.0 mmHg in group 2 and there was no significant difference. The pressure response to ICV choline became evident within 1 min and reached a maximum magnitude in 10 min in both groups. Compared to the sham operated rats (group 2), the pressure response to ICV choline was significantly attenuated in sympathectomized rats (p < 0.05). However, the plasma vasopressin levels were not significantly affected by ICV choline or a cervical sympathectomy. CONCLUSIONS: While the unilateral cervical sympathectomy itself did not have any effect on bloodpressure, it attenuated the pressure response to ICV choline. A unilateral cervical sympathectomy may attenuate the hypertensive response which is caused by an increased central cholinergic neurotransmission.

Effects of Intrathecal Magnesium Sulphate in a Rat Model of Postoperative Pain / 대한마취과학회지

BACKGROUND: The mechanical hyperalgesia that follows peripheral tissue injury results from peripheral and central sensitization. Central sensitization is initiated and maintained by windup that can be prevented by N-methyl-D-aspartate (NMDA) antagonists. NMDA antagonists, therefore, have the potential to prevent and treat pain, although clinical uses are limited because of their side effects. This study was designed to evaluate the analgesic action of intrathecal (IT) magnesium sulphate in a rat model of postoperative pain and investigate the analgesic mechanism of magnesium. METHODS: Forty-two Sprague-Dawley rats (300 +/- 20 g) were prepared with a chronic IT catheter. Under brief enflurane anesthesia, a 1-cm incision including skin, muscle and fascia was made in the plantar aspect of the hind paw and closed. Normal saline, magnesium (30, 100, 300, 600 microgram), NMDA 50 ng or NMDA 50 ng with magnesium 300 microgram was administered via the IT catheter after recovery. Response frequency, using Von Frey filaments, cumulative pain scores and motor deficits were assessed. RESULTS: The mechanical hyperalgesia and nonevoked pain behaviors decreased significantly at 1 h or 1 h and 3 h after IT injection of magnesium 100 microgram or 300 microgram compared to the saline group without profound motor deficits in a rat model of postoperative pain. However, the rats administered with magnesium 600 microgram were lethargic due to severe motor weakness. Effective duration of magnesium decreased significantly in the group of NMDA 50 ng with magnesium 300 microgram compared to that of magnesium 300 microgram administered alone, but the initial effects were similar between the two groups. CONCLUSIONS: We conclude that IT magnesium sulphate can modulate nociceptive processing after tissue injury and the analgesic mechanism of magnesium is involved in NMDA receptors. Magnesium,therefore, may offer a therapeutic agent for postoperative pain and may be an agent that prevents postoperative pain from changing to persistent pathological pain.

The Analgesic Effect of Intrathecal Gabapentin in a Rat Model of Incisional Pain / 대한마취과학회지

BACKGROUND: Gabapentin, an anticonvulsant structurally related to gamma-aminobutyric acid (GABA), was recently reported to be effective in pain associated with reflex sympathetic dystrophy and neuropathy. However, the effects of intrathecal (IT) gabapentin in postoperative pain are unclear. This study was designed to evaluate the analgesic action of IT gabapentin in a rat model of postoperative pain which was similar to human postoperative pain states. METHODS: Rats were prepared with chronic intrathecal catheter. Under halothane anesthesia, a 1 cm incision was made in the plantar aspect of the hind paw and closed. Rats were divided into 7 groups, a control group (saline 20 microliter intrathecally n = 6); a GP 30 group (gabapentin 30 microgram intrathecally, n = 6); a GP 100 group (gabapentin 100 microgram intrathecally, n = 6); a GP 300 group (gabapentin 300 microgram intrathecally, n = 6); a GP 1000 group (gabapentin 1,000 microgram intrathecally, n = 6); a NS-GP group (saline 10 microliter and gabapentin 300 microgram intrathecally, n = 6) and DS-GP group (D-serine 100 microgram and gabapentin 300 microgram intrathecally, n = 6). The rats were placed on an elevated plastic mesh floor, and withdrawal threshold was determined using calibrated von Frey filaments applied from beneath the test cage to an area adjacent to the wound. A cumulative pain score based on the weight bearing behavior of the rats, and motor deficit score, were also assessed. RESULTS: In all group, the median withdrawal threshold for punctate hyperalgesia decreased from 148.4 mN before surgery to 1.5 mN-14.5 mN 2 hours after surgery-inducing hyperalgesia and remained unchanged during the 2hr testing period. The IT administration of gabapentin (30 300 microgram) increased the median withdrawal threshold toward preincision values dose-dependently and the nonevoked pain scores were also decreased. But the effects of intrathecal gabapentin were reversed by IT D-serine. The Analgegic effects of gabapentin were observed at doses that had no significant effect on motor function or spontaneous activity. CONCLUSIONS: These observations suggest that intrathecal gabapentin can modulate the facilitation of spinal nociceptive processing by tissue injury and may offer a therapeutic agent for the treatment of postoperative pain.

Prader-Willi Syndrome: A case report / 대한마취과학회지

In 1956, Prader and Willi first described a clinical syndrome that included severe neonatal hypotonia, hyperphagia, obesity, diabetes, hypogonadism, cryptorchidism, dental caries and mental deficiency. We have anesthetized a male patient who had Prader-Willi syndrome. He suffered for both pyoknee. General anesthesia was performed using N2O-O2-isoflurane. During induction and maintenance of anesthesia, we focused on the airway management, hypotonia, abnormal glucose metabolism, protection of aspiration and cardiovascular stabilization. Emergence of anesthesia was unremarkable. But he was expired from sepsis on the fourth postoperative day.

Effects of Preemptive Intrathecal Bupivacaine on Postoperative Pain in Rats / 대한마취과학회지

BACKGROUND: Preemptive analgesia is an antinociceptive treatment that prevents the development of central sensitization which contributes to the post-injury pain hypersensitivity. But controversies exist over the effectiveness and clinical value of preemptive analgesia. The aim of this study is to evaluate the preemptive effect of intrathecal bupivacaine on incisional pain in rats. METHODS: Thirty male rats were divided into 3 groups, saline-treated control group (n=10), post-treatment group (n=10), and pre-treatment group (n=10) according to the time which intrathecal administration of bupivacaine was done. To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal frequency and withdrawal thresholds were measured by von Frey filaments at 30 min, 1 hr, 2 hrs, 3 hrs, 1 day, 3 days and 7 days after incision. RESULTS: In control group, the withdrawal frequency increased from 0+/-0% before incision to 98.0+/-1.3% after the foot incision and the responses gradually declined during the postoperative 7 days to 52.0+/-4.7%. The median withdrawal threshold decreased from 148.43 mN before incision to 0.05 mN after foot incision and gradually increased during the postoperative 7 days to 6.79 mN. The post-treatment group showed no significant differences in the withdrawal frequency and withdrawal thresholds when compared with control group at post-operative 1 hour and thereafter (P<0.05). The pre-treatment group showed significantly lower withdrawal frequency and significantly higher withdrawal threshold compared with control group at postoperative 30 min and thereafter (P<0.05), and significantly lower withdrawal frequency and higher withdrawal threshold compared with post-treatment group at postoperative 2 hours and thereafter (P<0.05). CONCLUSION: We conclude that intrathecal bupivacaine administered before incision reduces postoperative delayed hyperalgesia in incisional pain model, and it may result from preventing the development of injury- induced central sensitization.

Effects of Preemptive Intrathecal Bupivacaine on Postoperative Pain in Rats / 대한마취과학회지

BACKGROUND: Preemptive analgesia is an antinociceptive treatment that prevents the development of central sensitization which contributes to the post-injury pain hypersensitivity. But controversies exist over the effectiveness and clinical value of preemptive analgesia. The aim of this study is to evaluate the preemptive effect of intrathecal bupivacaine on incisional pain in rats. METHODS: Thirty male rats were divided into 3 groups, saline-treated control group (n=10), post-treatment group (n=10), and pre-treatment group (n=10) according to the time which intrathecal administration of bupivacaine was done. To evaluate postoperative mechanical hyperalgesia in injured feet, withdrawal frequency and withdrawal thresholds were measured by von Frey filaments at 30 min, 1 hr, 2 hrs, 3 hrs, 1 day, 3 days and 7 days after incision. RESULTS: In control group, the withdrawal frequency increased from 0+/-0% before incision to 98.0+/-1.3% after the foot incision and the responses gradually declined during the postoperative 7 days to 52.0+/-4.7%. The median withdrawal threshold decreased from 148.43 mN before incision to 0.05 mN after foot incision and gradually increased during the postoperative 7 days to 6.79 mN. The post-treatment group showed no significant differences in the withdrawal frequency and withdrawal thresholds when compared with control group at post-operative 1 hour and thereafter (P<0.05). The pre-treatment group showed significantly lower withdrawal frequency and significantly higher withdrawal threshold compared with control group at postoperative 30 min and thereafter (P<0.05), and significantly lower withdrawal frequency and higher withdrawal threshold compared with post-treatment group at postoperative 2 hours and thereafter (P<0.05). CONCLUSION: We conclude that intrathecal bupivacaine administered before incision reduces postoperative delayed hyperalgesia in incisional pain model, and it may result from preventing the development of injury- induced central sensitization.

A Case of Rupture of Right Common Iliac Artery and Vein during Lumbar Discectomy: A case report / 대한구급학회지

Intraabdominal vascular complications associated with lumbar disc surgery are rare but have potentially fatal consequences. Clinical manifestations of such injuries may be extremely variable and confused with anesthetic complications, myocardial infarction, or pulmonary embolism. So, the presence of vascular injury may not be recognized immediately. Recently, we experienced a case of extensive retroperitoneal hemorrhage during lumbar disc surgery. The patient was a 35 year-old healthy female. During operation, unexplained profound hypotension and tachycardia developed, but abnormal bleeding was not seen in the operative wound. Emergency CT of the abdomen was performed, and huge retroperitoneal hematoma was confirmed by the CT scan. Immediate abdominal exploration revealed the injury to right common iliac artery and vein. The patient underwent primary repair of lacerated artery and vein. Postoperative recovery was uneventful. We think awareness of the likelihood of vascular complications related to disc surgery is quite important for early diagnosis and management of these life-threatening complications.