Ultimo Aggiornamento: Gennaio 2004

1: Br J Anaesth. 2003 Dec;91(6):836-41.

Randomized prospective study of the analgesic effect of nefopam after
orthopaedic surgery.

Du Manoir B, Aubrun F, Langlois M, Le Guern ME, Alquier C, Chauvin M, Fletcher
D.

Service d'Anesthesie Reanimation, Hopital Raymond-Poincare, Garches, France.

BACKGROUND: Balanced postoperative analgesia combines non-narcotic drugs and
opioids. We organized a large study to evaluate nefopam analgesia and tolerance
in combination with morphine for patient-controlled analgesia (PCA) after
orthopaedic surgery. METHODS: Two hundred and one patients scheduled to undergo
hip arthroplasty were included in this multicentre (n=24), double-blind,
randomized study comparing nefopam (20 mg every 4 h for 24 h) with placebo, the
first dose being infused peroperatively. The primary outcome measure was the
cumulative morphine dose received postoperatively by PCA over 24 h. Secondary
outcome measures were the amount of morphine received as a loading dose in the
postanaesthesia care unit (PACU) and during the 24-h observation period, and
pain assessments using a visual analogue scale (VAS) and a verbal pain scale
(VPS), patient's satisfaction with analgesia and treatment tolerance. RESULTS:
The two groups were comparable with respect to their characteristics and
preoperative pain assessment. PCA-administered morphine over 24 h was
significantly less for the nefopam group than the control group (21.2 (15.3) and
27.3 (19.2) mg respectively; P=0.02). This morphine-sparing effect was greater
(35.1%) for patients with severe preoperative pain (VAS>30/100). For the entire
study period (loading dose and PCA), morphine use was less for the nefopam group
(34.5 (19.6) vs 42.7 (23.6) mg; P=0.01). Pain VAS at PACU arrival and during the
whole PACU period was significantly lower for the nefopam than for the placebo
group (P=0.002 and 0.04 respectively). Patient satisfaction was similar for the
nefopam and placebo groups. CONCLUSION: In combination with PCA morphine,
nefopam gives significant morphine-sparing with lower immediate postoperative
pain scores without major side-effects. This analgesic effect seems to be
particularly notable for patients with intense preoperative pain.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled TrialPMID: 14633755 [PubMed - indexed for MEDLINE]

2: Br J Anaesth. 2003 Dec;91(6):830-5.

Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after
joint replacement surgery.

Bianconi M, Ferraro L, Traina GC, Zanoli G, Antonelli T, Guberti A, Ricci R,
Massari L.

Department of Anesthesiology and Intensive Care, St Anna Hospital Ferrara,
Ferrara, Italy.

BACKGROUND: As continuous wound instillation with local anaesthetic has not been
evaluated after hip/knee arthroplasties, our study was designed to determine
whether this technique could enhance analgesia and improve patient outcome after
joint replacement surgery. METHODS: Thirty-seven patients undergoing elective
hip/knee arthroplasties under spinal block were randomly assigned to two
analgesia groups. Group M received continuous i.v. infusion of morphine plus
ketorolac for 24 h. Then, a multi-hole 16 G catheter was placed subcutaneously
and infusion of saline was maintained for 55 h. Group R received i.v. saline.
Thereafter the wound was infiltrated with a solution of ropivacaine 0.5% 40 ml,
then a multi-hole 16 G catheter was placed subcutaneously and an infusion of
ropivacaine 0.2% 5 ml h(-1) was maintained for 55 h. Visual analogue scale
scores were assessed at rest and on passive mobilization by nurses blinded to
analgesic treatment. Total plasma ropivacaine concentration was measured.
RESULTS: Group R showed a significant reduction in postoperative pain at rest
and on mobilization, while rescue medication requirements were greater in Group
M. Total ropivacaine plasma concentration remained below toxic concentrations
and no adverse effects occurred. Length of hospital stay was shorter in Group R.
CONCLUSION: Infiltration and wound instillation with ropivacaine 0.2% is more
effective in controlling postoperative pain than systemic analgesia after major
joint replacement surgery.

Publication Types:
Clinical Trial
Randomized Controlled TrialPMID: 14633754 [PubMed - indexed for MEDLINE]

3: J Clin Oncol. 2003 Dec 1;21(23):4261-2. Epub 2003 Oct 27.

Comment on:
J Clin Oncol. 2003 Dec 1;21(23):4277-84.Bisphosphonates for men with prostate cancer: sifting through the rubble.

Kelly WK, Steineck G.

Publication Types:
Comment
EditorialPMID: 14581442 [PubMed - indexed for MEDLINE]

4: J Pain Symptom Manage. 2004 Jan;27(1):79-84.

Punctate midline myelotomy for intractable visceral pain caused by hepatobiliary
or pancreatic cancer.

Hwang SL, Lin CL, Lieu AS, Kuo TH, Yu KL, Ou-Yang F, Wang SN, Lee KT, Howng SL.

Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan.

The purpose of this study was to demonstrate the existence of a newly recognized
midline posterior column pathway that mediates the perception of visceral pain
resulting from hepatobiliary or pancreatic cancer. A punctate midline myelotomy
(PMM) of T(3) level was performed in 6 patients who experienced severe visceral
pain caused by hepatobiliary or pancreatic cancer. Preoperatively, the pain was
refractory to strong opioids. Clinical efficacy of PMM was evaluated by
comparing patient pain rating on a visual analogue scale. Follow-up periods
ranged from 2-18 weeks after operation. All 6 patients had immediate pain relief
after operation. Although the pain recurred from 2-12 weeks later in 3 patients,
the severity of recurrent cancer pain markedly decreased. No adverse
neurological sequelae were observed. Our results of high thoracic PMM offer
clinical support for the concept that neurosurgical interruption of midline
visceral pain pathway can effectively control severe visceral pain without
causing adverse neurological sequelae in patients with hepatobiliary or
pancreatic cancer.

PMID: 14711472 [PubMed - in process]

5: J Pain Symptom Manage. 2004 Jan;27(1):72-8.

Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case
report.

Cata JP, Cordella JV, Burton AW, Hassenbusch SJ, Weng HR, Dougherty PM.

Department of Symptom Research, University of Texas M. D. Anderson Cancer
Center, Houston, Texas 77030, USA.

We present two patients with chemotherapy-induced painful neuropathy that had
been poorly controlled with medications but successfully treated with spinal
cord stimulation (SCS). A trial period of SCS provided effective pain relief in
both patients who subsequently underwent permanent stimulator implantation.
Psychophysical tests were performed before and after the implantation of trial
and permanent stimulators. SCS improved pain scores and facilitated a reduction
of medications. Both patients reported improved gait and one of them also
reported an increase in leg flexibility. Psychophysical tests demonstrated an
improvement in touch and sharpness detection thresholds. In summary, SCS offers
a therapeutic option for patients with chemotherapy-induced peripheral
neuropathy who have poor pain relief with standard medical treatment.

PMID: 14711471 [PubMed - in process]

6: J Pain Symptom Manage. 2004 Jan;27(1):61-71.

Effects of a continuing education program on nurses' practices of cancer pain
assessment and their acceptance of patients' pain reports.

Ger LP, Chang CY, Ho ST, Lee MC, Chiang HH, Chao CS, Lai KH, Huang JM, Wang SC.

Department of Medical Education and Research, Kaohsiung Veterans General
Hospital, Kaohsiung, Taiwan.

A hospital-based quasi-experimental (pretest and post-test) study was conducted
in Kaohsiung Veteran General Hospital, Taiwan. This study was to evaluate a
continuing education program (CEP) on nurses' practices of cancer pain
assessment and their acceptance of patients' pain reports with respect to four
types of misconceptions. A questionnaire was sent to on-duty nurses or head
nurses with patient care responsibilities before the implementation of CEP
(n=645) and six months after the program (n=630). The response rates were 92.6%
and 91.3% for pretest and post-test surveys, respectively. The CEP was
implemented in 8 weeks with four-repeated sessions of 4-hour lectures. A one-day
workshop focused on cancer pain assessment and treatment was held 3 months after
the four-repeated sessions. Several educational strategies and teaching
materials were used in the CEP. The results showed that CEP made statistically
significant yet moderate improvement in nurses' practices of pain assessment
using pain rating scales (pretest 3.29+/-0.76 vs. post-test 3.48+/-0.75,
P<0.001) and acceptance of patient's pain reports without misconceptions on
addiction (3.12+/-0.80 vs. 3.39+/-0.90, P<0.001), phantom pain (3.91+/-0.96 vs.
4.07+/-0.92, P=0.005), and placebo testing (3.63+/-0.72 vs. 3.81+/-0.73,
P<0.001), except on patient gender-age-related doubts (3.60+/-0.72 vs.
3.67+/-0.77, P=0.109). In order to achieve further improvement, additional
follow-up CEP combined with a hospital-wide institutionalization of pain
assessment should be promoted and implemented in the future.

PMID: 14711470 [PubMed - in process]

7: J Pain Symptom Manage. 2004 Jan;27(1):1-3.

Pain management in cancer patients with bone metastases remains a challenge.

Yau V, Chow E, Davis L, Holden L, Schueller T, Danjoux C.

Publication Types:
LetterPMID: 14711462 [PubMed - in process]

8: JAMA. 2004 Jan 7;291(1):63-70.

Intrathecal ziconotide in the treatment of refractory pain in patients with
cancer or AIDS: a randomized controlled trial.

Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M,
Fisher R, Bryce DA, Mangieri EA, Luther RR, Mayo M, McGuire D, Ellis D.

Division of Pain Medicine, Johns Hopkins University School of Medicine,
Baltimore, Md 21205, USA. pstaats@jhmi.edu

CONTEXT: Ziconotide (formerly SNX-111) selectively blocks N-type
voltage-sensitive calcium channels and may be effective in patients with pain
that is refractory to opioid therapy or those with intolerable opioid-related
adverse effects. OBJECTIVE: To assess the safety and efficacy of intrathecal
ziconotide in patients with pain that is refractory to conventional treatment.
DESIGN, SETTING, AND PATIENTS: Double-blind, placebo-controlled, randomized
trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in
the United States, Australia, and the Netherlands. Patients were 111 individuals
ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain
Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in
a 2:1 ratio to receive ziconotide or placebo treatment. INTERVENTIONS:
Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day
maintenance phase for responders and crossover of nonresponders to the opposite
treatment group. MAIN OUTCOME MEASURE: Mean percentage change in VASPI score
from baseline to the end of the initial titration period. RESULTS: Of the
evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38
(95%) of 40 patients receiving placebo were taking opioids at baseline (median
morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for
the placebo group; P =.63, based on mean values), and 36 had used intrathecal
morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and
77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1%
(95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1%
(95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of
ziconotide in the maintenance phase. Pain relief was moderate to complete in
52.9% of patients in the ziconotide group compared with 17.5% in the placebo
group (P<.001). Five patients receiving ziconotide achieved complete pain
relief, and 50.0% of patients receiving ziconotide responded to therapy compared
with 17.5% of those receiving placebo (P =.001). CONCLUSION: Intrathecal
ziconotide provided clinically and statistically significant analgesia in
patients with pain from cancer or AIDS.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled TrialPMID: 14709577 [PubMed - indexed for MEDLINE]

9: JAMA. 2004 Jan 7;291(1):43-4; author reply 44.

Comment on:
JAMA. 2003 Sep 17;290(11):1474-8.Magnets for patients with heel pain.

Weintraub MI.

Publication Types:
Comment
LetterPMID: 14709572 [PubMed - indexed for MEDLINE]

10: N Engl J Med. 2004 Jan 8;350(2):166-76.

Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 1-2004. A 49-year-old woman with asymmetric painful neuropathy.

Chad DA, Hedley-Whyte ET.

Department of Neurology, UMass Memorial Health Care, Worcester, USA.

Publication Types:
Case Reports
Clinical ConferencePMID: 14711916 [PubMed - indexed for MEDLINE]

11: Pain. 2003 Oct;105(3):499-506.

QTc interval prolongation associated with intravenous methadone.

Kornick CA, Kilborn MJ, Santiago-Palma J, Schulman G, Thaler HT, Keefe DL,
Katchman AN, Pezzullo JC, Ebert SN, Woosley RL, Payne R, Manfredi PL.

Pain and Palliative Care Service, Department of Neurology, Memorial
Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
kornick@riversidespine.com

Numerous medications prolong the rate-corrected QT (QTc) interval and induce
arrhythmias by blocking ionic current through cardiac potassium channels
composed of subunits expressed by the human ether-a-go-go-related gene (HERG).
Recent reports suggest that high doses of methadone cause torsades de pointes.
To date, no controlled study has described an association between methadone and
QTc prolongation. The only commercial formulation of parenteral methadone
available in the United States contains the preservative chlorobutanol. The
objectives of this study are to determine: (1) whether the administration of
intravenous (i.v.) methadone causes QTc prolongation in humans; (2) whether
methadone and/or chlorobutanol block cardiac HERG potassium currents (IHERG) in
vitro. Over 20 months, we identified every inpatient with at least one
electrocardiogram (ECG) performed on i.v. methadone. For each patient, we
measured QTc intervals for every available ECG performed on and off i.v.
methadone. Concurrent methadone doses were also recorded. Similar data were
collected for a separate group of inpatients treated with i.v. morphine. In a
separate set of experiments IHERG was evaluated in transfected human embryonic
kidney cells exposed to increasing concentrations of methadone, chlorobutanol,
and the two in combination. Mean difference (+/- standard error) per patient in
QTc intervals on and off methadone was 41.7 (+/- 7.8)ms, p<0.0001. Mean
difference in QTc intervals on and off morphine was 9.0 (+/- 6.1)ms, p=0.15. The
approximately linear relationship between QTc measurements and log-dose of
methadone was significant (p<0.0001). Methadone and chlorobutanol independently
block IHERG in a concentration-dependent manner with IC50 values of 20 +/- 2
microM and 4.4 +/- 0.3 mM, respectively. Chlorobutanol potentiates methadone's
ability to block IHERG. Methadone in combination with chlorobutanol is
associated with QTc interval prolongation. Our data strongly suggest that
methadone in combination with chlorobutanol is associated with QTc interval
prolongation.

PMID: 14527710 [PubMed - indexed for MEDLINE]

12: Pain. 2003 Oct;105(3):481-8.

Analgesic and placebo effects of thalamic stimulation.

Marchand S, Kupers RC, Bushnell MC, Duncan GH.

Faculte de Medecine, Neurochirurgie, Universite de Sherbrooke, 3001 12e Avenue
Nord, Sherbrooke, QC, Canada J1H 5N4. serge.marchand@usherbrooke.ca

Numerous clinical studies have reported successful relief of chronic pain with
sensory thalamic stimulation. However, even with the extensive use of sensory
thalamic stimulation as a clinical tool in the relief of chronic pain, the
results are still inconsistent. This discrepancy could probably be explained by
the fact that the majority of these studies are case reports or retrospective
analyses, which have often used imprecise pain measurements that do not allow a
rigorous statistical evaluation of pain relief. None of these studies measured
the effect of stimulation on clinical pain for longer than a few hours per day,
which is an important aspect considering that clinical pain can vary over time.
Moreover, placebo controls are seldom included. In the current study, we
measured patients' pain perception at home over a 2-week period, both during
days of normal stimulation of the sensory thalamus and during days without
stimulation. Patients also came to the laboratory to assess the effects of
thalamic and placebo stimulation on clinical pain, experimental heat pain,
innocuous air puff and visual stimulation. A potential relation between the
perceived paresthesia and analgesic efficacy during thalamic and placebo
stimulation was also explored. We found that thalamic stimulation significantly
affected clinical and experimental pain perception, but that an important
placebo component also exists. On the other hand, neither thalamic nor placebo
stimulation affected air puff and visual ratings, suggesting that the effect
applies specifically to pain and hence is not caused by a general change in
attention. The level of paresthesia elicited during the placebo manipulation was
also directly correlated with the degree of placebo pain relief. These results
suggest that thalamic stimulation produces a small but significant reduction in
pain perception, but that a significant placebo effect also exists.

PMID: 14527708 [PubMed - indexed for MEDLINE]