Steady-State Pharmacokinetics of Intravenous Hydromorphone in Japanese Patients With Renal Impairment and Cancer Pain.

Background: The opioid analgesic hydromorphone has a low renal excretion ratio; however, exposure after oral administration is several times higher in those with moderate or severe renal impairment. Objectives: We evaluated the impact of renal impairment on the steady-state pharmacokinetics of intravenously administered hydromorphone in patients with cancer being treated for pain. Design: This was an open-label, prospective, parallel-comparison, interventional clinical pharmacology study. Setting/Subjects: This study was conducted at one hospital in Japan. Using creatinine clearance (CLcr) values, patients were grouped according to kidney function: CLcr ≥90 mL/min (normal), 60-<90 mL/min (mild impairment), 30-<60 mL/min (moderate impairment), or <30 mL/min (severe impairment). Measurements: Hydromorphone was administered by constant infusion to patients at the same constant dose rate as at the time of enrollment. Hydromorphone and its glucuronide metabolite concentrations in plasma and urine were measured by liquid chromatography-mass spectrometry. Pharmacokinetic parameters at steady state were assessed using noncompartmental analysis. Results: Thirty-two patients were enrolled (normal, n = 3; mild, n = 10; moderate, n = 15; and severe, n = 4). Adjusted geometric mean ratios for hydromorphone steady-state clearance (CLss) for patients with impaired versus normal renal function were 0.69 (90% confidence interval [CI], 0.41-1.14), 0.52 (90% CI, 0.31-0.84), and 0.55 (90% CI, 0.30-1.02) for mild, moderate, or severe impairment, respectively. Exposures to the metabolite hydromorphone-3-glucuronide generally increased with renal impairment. No adverse event was reported. Conclusion: Hydromorphone CLss in patients with impaired renal function (moderate and severe) was decreased ∼50% of that of normal renal function.

Adhesion-induced chronic abdominal pain: a case report on the diagnostic value of Carnett's test.

BACKGROUND: Chronic abdominal pain is a common clinical problem. However, diagnosing chronic abdominal pain often requires detailed diagnostic evaluations in addition to sufficient history taking and physical examination, owing to its uncertain etiology. CASE PRESENTATION: We report a case of a 36-year-old man with chronic abdominal pain originating from postoperative adhesions. Postoperative adhesions are common phenomena, and abdominal surgery can cause severe abdominal pain, the source of which can be difficult to detect. Carnett's test is useful to detect abdominal wall tenderness and to determine the affected abdominal quadrant. Incorporating its use with a detailed chronological clinical history contributes to the improvement of diagnostic accuracy. In addition to the above-mentioned information, attention to subtle imaging findings may provide greater diagnostic accuracy. CONCLUSIONS: Abdominal pain induced by postoperative adhesions was reduced by laparoscopic adhesiolysis. Carnett's test is an effective tool for evaluating pain and detecting its cause.

A case of severe headache attributed to vertebral artery dissection.

BACKGROUND: Vertebral artery dissection (VAD) sometimes has no specific symptoms and is difficult to differentiate from other forms of headache. CASE PRESENTATION: A woman in her thirties had a severe, throbbing left-sided headache. A migraine without aura was suspected and zolmitriptan was administered, which alleviated the symptoms. The woman was consequently deemed to have a migraine without aura. Despite the lack of abnormal neurological findings and showed no abnormalities on cranial computed tomography, her symptoms were not typical for migraines and showed little improvement with therapy. She therefore underwent a cranial magnetic resonance imaging (MRI) examination, which revealed VAD, for which she was transferred to the department of neurosurgery for conservative treatment. CONCLUSION: The possibility of vertebral artery dissection should be considered in the differential diagnosis of severe secondary headaches, and prompt diagnosis and treatment based on detailed MRI and magnetic resonance angiography examinations should be performed.

[Opioid Therapy and Management of Side Effects Associated with Opioids].

Opioids are very useful medications to reduce suffering of cancer patients such as refractory pain and dyspnea. We physicians have to use opioids to have good management of pain and suffering associated with cancer including management of side effects caused by opioids. Opioids couple opioid receptors and affect several pharmacological effects. Other than analgesic effect, opioids have some side effects of constipation, nausea and vomiting, respiratory depression. In this chapter, I take important side effects of constipation, nausea and vomiting and respiratory depression. Next, serotonin syndrome caused by tramadol combined with anti-depressants is remarked as assignable syndrome. As advancing in chemotherapy for cancer treatment, cancer survivors live longer with opioid therapy. We have to pay attention to the side effects and another dysfunction caused by long use of opioids. It is important that we physician use opioids effectively to keep activity of daily living(ADL) of patients and families as team approach.

Retention of finger blood flow against postural change as an indicator of successful sympathetic block in the upper limb.

BACKGROUND: Sympathetic block in the upper limb has diagnostic, therapeutic and prognostic utility for disorders in the upper extremity that are associated with sympathetic disturbances. Increased skin temperature and decreased sweating are used to identify the adequacy of sympathetic block in the upper limb after stellate ganglion block (SGB). Baroreflexes elicited by postural change induce a reduction in peripheral blood flow by causing sympathetic vasoconstriction. We hypothesized that sympathetic block in the upper limb reduces the decrease in finger blood flow caused by baroreflexes stimulated by postural change from the supine to long sitting position. This study evaluated if sympathetic block of the upper limb affects the change in finger blood flow resulting from postural change. If change in finger blood flow would be kept against postural changes, it has a potential to be a new indicator of sympathetic blockade in the upper limb. METHODS: Subjects were adult patients who had a check-up at the Department of Pain Management in our university hospital over 2 years and 9 months from May 2012. We executed a total of 91 SGBs in nine patients (N=9), which included those requiring treatment for pain associated with herpes zoster in seven of the patients, tinnitus in one patient and upper limb pain in one patient. We checked for the following four signs after performing SGB: Horner's sign, brachial nerve blockade, finger blood flow measured by a laser blood flow meter and skin temperature of the thumb measured by thermography, before and after SGB in the supine position and immediately after adopting the long sitting position. RESULTS: We executed a total of 91 SGBs in nine patients. Two SGBs were excluded from the analysis due to the absence of Horner's sign. We divided 89 procedures into two groups according to elevation in skin temperature of the thumb: by over 1°C (sympathetic block group, n=62) and by <1°C (nonsympathetic block group, n=27). Finger blood flow decreased significantly just after a change in posture from the supine to long sitting position after SGB in both groups. In the sympathetic block group, the ratio of finger blood flow in the long sitting position/supine position with a change in posture significantly increased after SGB compared with before SGB (before SGB: range 0.09-0.94, median 0.53; after SGB: range 0.33-1.2, median 0.89, p<0.0001). CONCLUSION: Our study shows that with sympathetic block in the upper limb, the ratio of finger blood flow significantly increases despite baroreflexes stimulated by postural change from the supine to long sitting position. Retention of finger blood flow against postural changes may be an indicator of sympathetic block in the upper limb after SGB or brachial plexus block.

[Taking an Active Part in a Palliative Care Unit as an Anesthesiologist].

Palliative care prevents and relieves total pain of patients and their families and improves their quality of life. The author describes the work of anesthesiologists in palliative care unit as ward staffs. The need for palliative care units is increasing and new palliative care units are being established throughout Japan. Anesthesiologists are involved in anesthesia, pain management intensive care, emergency medicine and palliative care. The anesthesiologists in palliative care are involved in use of opioid and nerve block for treating physical pain. Sedatives such as minor tranquilizer to sedate a patient under regional anesthesia are used by anesthesiologists in operating rooms. Anesthesiologists manage the patients who need to be sedated for relief of refractory sufferings by sedative drugs in palliative care unit It is important that we anesthesiologists walk alongside the patients when they need to be heard in the end of life stage. We expect that it is a key point to palliate spiritual pain of the patients. I hope many young anesthesiologists serve as capable members in the palliative care unit in the future.

Fentanyl tolerance in the treatment of cancer pain: a case of successful opioid switching from fentanyl to oxycodone at a reduced equivalent dose.

Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 µg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.

[Case of spinal epidural abscess after continuous epidural block to manage the pain of herpes zoster].

A woman in her 90's received continuous epidural block for the pain of herpes zoster. Four days after epidural catheterization, she was found with cellutitis. Fourteen days after epidural catheterization, spinal epidural abscess was pointed out on MRI. Since there were no neurological symptoms, we performed conservative medical management with antibiotics. She recovered without sequela When the symptoms of cellutitis appeared after epidural block (even if there are neither neurological symptoms nor infectious signs), there is a possibility of progressing into spinal epidural abscess.

Effects of epidural anesthesia with 0.2% and 1% ropivacaine on predicted propofol concentrations and bispectral index values at three clinical end points.

STUDY OBJECTIVE: To compare the effects of 0.2% epidural ropivacaine and those of 1% epidural ropivacaine on predicted propofol concentrations and bispectral index scores (BISs) at three clinical end points. DESIGN: Randomized double-blind study. SETTING: University hospital. PATIENTS: Thirty-five (35) ASA physical status I and II patients scheduled for elective surgery of the lower abdomen. INTERVENTIONS: Patients were randomly divided into 2 groups to receive epidurally 8 mL of 0.2% or 1% ropivacaine followed by the same solution at a rate of 6 mL/h. MEASUREMENTS: Twenty minutes after starting ropivacaine, a target-controlled infusion of propofol was started to provide a predicted blood concentration of 3 microg/mL; it increased by 0.5 microg/mL every 60 seconds until all 3 clinical end points were reached, as follows: P1, when patients lost consciousness; P2, when patients failed to show pupillary dilation and skin vasomotor reflex to transcutaneous electric stimulation applied to the upper level of loss of cold sensation; and P3, when patients failed to show pupillary dilation and skin vasomotor reflex to transcutaneous electric stimulation applied to C5. MAIN RESULTS: The effective concentration 50 values for both predicted blood and effect-site propofol concentrations were significantly larger in the 0.2% group than in the 1% group at all end points. The BIS at every end point was significantly smaller in the 0.2% group than in the 1% group. CONCLUSIONS: During combined epidural-propofol anesthesia, unconsciousness and lack of response to noxious stimulation occurred at lower predicted concentrations with 1% epidural ropivacaine than with 0.2% epidural ropivacaine. The results also suggest that the BIS may not be a good indicator when propofol anesthesia is combined with epidural anesthesia.

Breath-holding spells in somatoform disorder.

Breath-holding spells (BHS) are commonly seen in childhood. However, there are no case reports of BHS occurring in adolescents or young adults. We report two young adult cases and discuss the pathogensis, both physically and psychologically. BHS occurred for 1-2 minutes after hyperventilation accompanied by cyanosis in both cases. Oxygen saturation was markedly decreased. Each patient had shown distress and a regressed state psychologically. These cyanotic BHS occurred after hyperventilation, and we considered that a complex interplay of hyperventilation followed by expiratory apnea increased intrathoracic pressure and respiratory spasm. Breath-holding spells can occur beyond childhood.