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The frequency and timing of respiratory depression in 1524 postoperative patients treated with systemic or neuraxial morphine.

STUDY OBJECTIVE: To describe the frequency and timing of intravenous patient-controlled analgesia (IV-PCA) or neuraxial morphine-induced postoperative respiratory depression. DESIGN: Audit of data captured by routine quality assurance of the acute pain protocols that were implemented by nurses performing routine postoperative care. SETTING: The surgical wards of a university-affiliated, 700-bed, tertiary hospital. PATIENTS AND INTERVENTIONS: In real time, the data of all patients enrolled into our Acute Pain Service (APS) were entered and stored in the APS database. Thereafter, patients who had received IV morphine via a PCA device or neuraxial morphine between January 1999 and December 2002 were isolated. From this subset, all patients in whom a respiratory rate (RR) less than 10 breaths per minute was recorded were retrieved. MEASUREMENTS AND MAIN RESULTS: From a total of 4500 patients, IV or neuraxial morphine was administered to 1524 patients. Eighteen (1.2%) cases of an RR less than 10 breaths per minute were recorded (13 patients, 4 patients, and 1 patient in the IV-PCA, daily epidural morphine, and single-dose intrathecal morphine groups, respectively). A direct correlation between intraoperative fentanyl administration and postoperative respiratory depression was demonstrated between the IV-PCA (P = 0.03) and epidural groups (P = 0.05). The time from IV-PCA initiation or last neuraxial morphine administration until the diagnosis of respiratory depression ranged between 2 hours and 31.26 hours and 2 hours and 12.15 hours, respectively. Ten (55.6%) patients received naloxone. CONCLUSION: Morphine-induced respiratory depression may occur at any time during the APS admission. However, the optimal frequency of intermittent RR monitoring is unknown. Furthermore, because multiple variables (age, sex, prior opioid administration, site of operation) may affect morphine-induced respiratory depression, further investigation must be performed to determine the ideal monitoring protocol.

Adolescent↗

Amikacin and colistin for treatment of Acinetobacter baumannii meningitis.

We report a case of a 52-year-old man with post-surgical meningitis due to a multi-drug resistant Acinetobacter baumannii. Despite therapy with intravenous amikacin and imipenem the meningitis progressed. Upon institution of combination therapy with amikacin by the intravenous and intrathecal (IT) routes, and intravenous colistin the patient experienced successful clinical and microbiological outcomes.

Acinetobacter Infections↗

Antibody directed against GD(2) produces mechanical allodynia, but not thermal hyperalgesia when administered systemically or intrathecally despite its dependence on capsaicin sensitive afferents.

Anti-GD(2) antibodies have been shown to be effective for immunotherapy of neuroblastoma and other GD(2) enriched malignancies. Infusion of anti-GD(2) antibodies frequently causes spontaneous pain and allodynia for the duration of the immunotherapy and occasionally longer lasting neuropathic pain. Bolus intravenous injection of anti-GD(2) in rats initiates mechanical allodynia as measured by withdrawal threshold of the hindpaws. In this study, thermal thresholds were measured prior to and for up to 6 h following systemic anti-GD(2) administration in adult rats. In addition, both thermal and mechanical thresholds were tested following intrathecal administration of anti-GD(2) and IgG(2a). Murine anti-GD(2) elicited mechanical allodynia when administered into either the vasculature or the intrathecal space. Effective systemic doses were 1--3 mg/kg as previously shown. Intrathecally, optimal doses ranged from 0.01 to 0.1 ng; a higher dose was ineffective. Thermal hyperalgesia was not observed via either route of administration. Intrathecal pretreatment 48--72 h prior to the experiment with capsaicin at doses sufficient to cause a 50% depletion of dorsal horn CGRP, caused a total blockade of the mechanical allodynia indicating an involvement of peptidergic fine afferent fibers. It is likely that the antibody reacts with an antigen on peripheral nerve and/or myelin to initiate its effect. The lack of observed thermal hyperalgesia is surprising especially in light of the capsaicin-associated blockade, however, it is consistent with several other immune system related models of pain.

Animals↗

The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats.

Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects.

Analgesics↗

The influence of regional spinal cord hypothermia on transcranial myogenic motor-evoked potential monitoring and the efficacy of spinal cord ischemia detection.

OBJECTIVE: Myogenic motor-evoked responses to transcranial electrical stimulation (transcranial myogenic motor-evoked potentials) can rapidly detect spinal cord ischemia during thoracoabdominal aortic aneurysm repair. Recent evidence suggests that regional spinal cord hypothermia increases spinal cord ischemia tolerance. We investigated the influence of subdural infusion cooling on transcranial myogenic motor-evoked potential characteristics and the time to detect spinal cord ischemia in 6 pigs. METHODS: Regional hypothermia was produced by subdural perfusion cooling. A laminectomy and incision of the dura were performed at L2 to advance 2 inflow catheters at L4 and L6, to cool the lumbar subdural space with saline solution. Two temperature probes were advanced at L3 and L5, and 1 cerebrospinal fluid pressure line was advanced at L4. Spontaneous cerebrospinal fluid outflow was allowed. Spinal cord ischemia was produced by clamping a set of critical lumbar arteries, previously identified by transcranial myogenic motor-evoked potentials and lumbar artery clamping. The time between the onset of ischemia and detection with transcranial myogenic motor-evoked potentials (amplitude < 25%) was determined at cerebrospinal fluid temperatures of 37 degrees C and 28 degrees C. Thereafter, the influence of progressive cerebrospinal fluid cooling on transcranial myogenic motor-evoked potential amplitude and latency was determined. RESULTS: The time necessary to produce ischemic transcranial myogenic motor-evoked potentials, after the clamping of critical lumbar arteries, was not affected at moderate subdural hypothermia (3.8 +/- 0.9 min) compared with subdural normothermia (3.2 +/- 0.5 min; P =.6). Thereafter, progressive cooling resulted in a transcranial myogenic motor-evoked potential amplitude increase at 28 degrees C to 30 degrees C and was followed by a progressive decrease. Response amplitudes decreased below 25% at 14.0 degrees C +/- 1.1 degrees C. The influence of cerebrospinal fluid temperature on transcranial myogenic motor-evoked potential amplitude was best represented by a quadratic regression curve with a maximum at 29.6 degrees C. In contrast, transcranial myogenic motor-evoked potential latencies increased linearly with decreasing subdural temperatures. CONCLUSIONS: Detection of spinal cord ischemia with transcranial myogenic motor-evoked potentials is not delayed at moderate subdural hypothermia in pigs. At a cerebrospinal fluid temperature of 28 degrees C, transcranial myogenic motor-evoked potential amplitudes are increased. Further cerebrospinal fluid temperature decreases result in progressive amplitude decreases and latency increases.

Animals↗

Effect of intrathecal baclofen on bladder and sphincter function.

A programmable baclofen pump was implanted in 7 patients for relief of severe spasticity. The patients experienced improvement in bladder and sphincter function. This system would seem to be of value in improving lower urinary tract function in patients with diseases that produce marked spasticity.

Baclofen↗

Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin.

BACKGROUND: Implantable pumps for the delivery of intrathecal morphine have become a common option for administering opiate medication for the management of pain in patients with terminal cancer. Options for treating chronic pain of non-malignant origin are more controversial. This study describes responses to intrathecal morphine administration for managing chronic pain in patients without an underlying malignancy. METHODS: Eleven patients between the ages of 29 and 81 years, nine with failed back syndrome (FBS) and two with neuropathic pain (NP) from other causes, were chosen from 15 consecutive individuals referred to neurosurgery clinic. The presenting levels of pain and a functional-economic outcome level were determined for each patient. Patients were admitted to the hospital for therapeutic trials and were assessed for the appropriateness of their analgesic response and for adverse responses to the medication. A morphine pump was implanted in five males and six females who were followed for up to 3 years. RESULTS: A good to excellent analgesic response was seen in 8 (73%) patients (6 FBS; 2 NP). In the remaining three patients (27%), the analgesic response was judged poor (3 FBS). In patients with FBS, the total effective response was 67%. Two patients experienced bladder dysfunction requiring pump removal. Other adverse effects of pump placement were rare. CONCLUSIONS: The morphine pump was found to be a viable alternative in the management of failed back syndrome. Its use in long-term therapy, however, is not without limitations and should be a last choice option.

Adult↗

Intrathecal morphine delivered via subcutaneous pump for intractable pain in pancreatic cancer.

BACKGROUND: Pain secondary to unresectable pancreatic cancer is frequently severe and extremely difficult to control with traditional methods of analgesia. This retrospective study reports the analgesic effects of intrathecal morphine sulfate by implanted infusion pumps in nine patients with unresectable adenocarcinoma of the pancreas. METHODS: Nine patients were implanted over a 2-year period. Preoperative morphine i.v. equivalents were a mean of 81.51 mg/day, with a range of 20-140 mg/day. Patients were hospitalized for a trial dose of 1-2 mg of intrathecal Duramorph, 1 mg/ml, via lumbar puncture to assess whether adequate pain relief could be achieved and whether there would be drug-related side effects. RESULTS: All patients who received a trial dose experienced excellent pain relief, and subsequently underwent implantation of a lumbar subarachnoid catheter and infusion pump during the same hospitalization. The mean number of days from diagnosis to pump implant was 119, with a range of 3-587 days. The mean maximum daily dose was 21.28 mg, with a range of 3-73.10 mg. No patient experienced respiratory depression or excess sedation which prevented achievement of pain control. Minor supplemental narcotic use was documented in three of the nine patients. Assessment of pain control was made by the level of activity and the analog pain scale, with 0 being no pain and 10 being the worst pain imaginable. All of the patients experienced good to excellent relief of pain. The mean duration of intrathecal morphine sulfate use until death was 137.3 days, with a range of 52-354 days. CONCLUSIONS: This series of nine patients indicates that long-term administration of intrathecal morphine via implanted infusion pump in patients with pancreatic cancer is both efficacious and safe. All patients and their families reported an improved quality of life with an increased level of activity.

Adenocarcinoma↗

Comparison of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia.

A retrospective comparison was made of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia; (1) intrathecal methotrexate only; (2) intermediate-dose methotrexate infusion and intrathecal methotrexate and, (3) 2400 rads cranial irradiation and intrathecal methotrexate. The incidence of primary meningeal relapse was statistically significantly lower in both standard-risk patients (age grear than 24 months and less than or equal to 120 months white-cell count less than 20,000) and increased-risk patients (age less than or equal to 24 months or greater than 120 months and/or white-cell count greater than 20,000) whose central-nervous-system prophylaxis included cranial irradiation. The disease-free and overall survival of irradiated increased-risk patients was significantly better than that of unirradiated increased-risk patients. The disease-free survival of standard-risk patients who received intermediate-dose methotrexate was statistically superior to that of the remaining standard-risk patients. There were no significant differences in overall survival between the three groups of standard-risk patients.

Adolescent↗

The development of tolerance to intrathecal morphine in rat models of visceral and cutaneous pain.

The development of tolerance to intrathecal morphine was studied in rats chronically implanted with intrathecal catheters connected to osmotic minipumps. Measures of cutaneous nociception were the hot plate (HP) and tail flick (TF) tests. Measures of visceral nociception were visceromotor (VM) responses to ramped colorectal distension (CRD) and cardiovascular (CV) responses to phasic colorectal distension. Tolerance to a continuous infusion of 6 or 20 nmol/h of morphine sulfate developed over 6 days. A significant reduction in the dose-dependent effects of intrathecal morphine in the TF and HP tests and VM and CV responses to CRD occurred in rats receiving continuous infusions of morphine. The development of tolerance to intrathecal morphine was similar in both cutaneous and visceral models.

Animals↗

The control of severe cancer pain by continuous intrathecal infusion and patient controlled intrathecal analgesia with morphine, bupivacaine and clonidine.

The management of severe cancer pain may be problematic in spite of recent advances in pain management. A small percentage of patients with severe intractable pain and/or intractable side effects may require more aggressive interventional pain management strategies including the administration of medications continuously by the intrathecal route. A variety of medications, including morphine, bupivacaine, and clonidine, may be used intrathecally for the control of cancer pain. Optimal use of these medications requires individual titration to the patient's needs. We describe a case of severe cancer pain where these medications were used successfully by continuous intrathecal infusion and patient controlled intrathecal analgesia.

Analgesia, Patient-Controlled↗