Denis C. Moriarty

Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis

Background: Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. Methods: In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Results: Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 ± 5 months (mean ± SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87–100%) and 82% (74–91%) at 24 months and 94% (87–100%) and 77% (68–87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). Conclusions: This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.

Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis.

Background:Regional anesthesia and analgesia attenuate or prevent perioperative factors that favor minimal residual disease after removal of the primary carcinoma. Therefore, the authors evaluated prostate cancer recurrence in patients who received either general anesthesia with epidural anesthesia/analgesia or general anesthesia with postoperative opioid analgesia. Methods:In a retrospective review of medical records, patients with invasive prostatic carcinoma who underwent open radical prostatectomy between January 1994 and December 2003 and had either general anesthesia–epidural analgesia or general anesthesia–opioid analgesia were evaluated through October 2006. The endpoint was an increase in postoperative prostate-specific antigen. Results:After adjusting for tumor size, Gleason score, preoperative prostate-specific antigen, margin, and date of surgery, the epidural plus general anesthesia group had an estimated 57% (95% confidence interval, 17–78%) lower risk of recurrence compared with the general anesthesia plus opioids group, with a corresponding hazard ratio of 0.43 (95% confidence interval, 0.22–0.83; P = 0.012) in a multivariable Cox regression model. Gleason score and tumor size (percent of prostate involved) were also independent predictors of recurrence (hazards ratios of 1.19 [1.08, 1.52], P = 0.004, and 1.17 [1.03, 1.34] for 10% size difference, P = 0.01, respectively). A similar association between epidural use and recurrence was obtained by comparing patients matched on the propensity to receive epidural versus general anesthesia. Conclusions:Open prostatectomy surgery with general anesthesia, substituting epidural analgesia for postoperative opioids, was associated with substantially less risk of biochemical cancer recurrence. Prospective randomized trials to evaluate this association seem warranted.

Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro

BACKGROUND Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia-analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro. METHODS Patients were randomized to receive propofol/paravertebral anaesthesia-analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured. RESULTS Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (-24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups. CONCLUSIONS Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia-analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery.

Background: Breast cancer is the most common malignancy in women. Surgery remains the most effective treatment. Several perioperative factors, including the surgical stress response, many anesthetics and opioids, adversely affect immune function. Regional anesthesia-analgesia attenuates perioperative immunosuppression. We tested the hypothesis that patients who receive combined propofol/paravertebral anesthesia-analgesia (propofol/paravertebral) exhibited reduced levels of protumorigenic cytokines and matrix metalloproteinases (MMPs) and elevated levels of antitumorigenic cytokines compared with patients receiving sevoflurane anesthesia with opioid analgesia (sevoflurane/opioid). Methods: Primary breast cancer surgery patients were randomized to propofol/paravertebral (n = 15) or sevoflurane/opioid (n = 17) and preoperative and postoperative serum concentrations of 11 cytokines (interleukin 1&bgr; [IL-1&bgr;], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon &ggr;, and tumor necrosis factor &agr;) and 3 MMPs (MMP-1, MMP-3, and MMP-9) were measured. Results: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathologic diagnosis. Pain scores were lower at 1 and 2 hrs with paravertebral analgesia compared with morphine but similar at 24 hrs. Patients in the propofol/paravertebral group showed a greater percentage decrease in postoperative compared with preoperative IL-1&bgr; (median [quartiles], −26% [−15% to −52%] versus −4% [−14% to 2%], P = 0.003), a significant attenuation in elevated MMP-3 (2% [−39% to 12%] versus 29% [23%-59%], P = 0.011) and MMP-9 (26% [13%-54%] versus 74% [50%-108%], P = 0.02), and a significant increase in IL-10 (10% [5%-33%] versus −15% [20% to −2%], P = 0.001) compared with sevoflurane/opioid group. No significantly different changes in IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, interferon &ggr;, tumor necrosis factor &agr;, or MMP-1 were observed between the 2 groups. Conclusions: Propofol/paravertebral anesthesia-analgesia for breast cancer surgery alters a minority of cytokines influential in regulating perioperative cancer immunity. Further evaluation is required to determine the significance of these observations.

Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly

PurposePostoperative cognitive dysfunction (POCD) is evident in 26% of elderly patients seven days after major non-cardiac surgery. Despite the growing popularity of day surgery, the influence of anesthetic techniques on next day POCD has not been investigated. Therefore, we evaluated the incidence of POCD and changes in serum markers of neuronal damage (S-100ß protein and Neuron-Specific Enolase), 24 hr after single-agent propofol or sevoflurane anesthesia in elderly patients undergoing minor surgery.MethodsPatients (n = 30, mean age 73, range 65–86 yr) coming for cystoscopy or hysteroscopy, were randomized, in an observer-blind design, to receive either single-agent propofol or sevoflurane anesthesia. Changes in neuropsychological tests (the Stroop test and the modified Word-Recall Test), 24 hr postoperatively were compared with age-matched control subjects (n = 15) using Z-score analysis. Changes in S-100ß protein and Neuron-Specific Enolase levels were also documented.ResultsPOCD was present in 7/15 [47% (95% confidence interval (CI) 21 to 72%)] patients who received propofol and 7/15 [47% (95% CI 21 to 72%)] patients who received sevoflurane, compared with 1/15 [7% (95% CI 6 to 19%)] control patients, P = 0.03. S-100ß protein and Neuron-Specific Enolase levels were not significantly different in anesthetized patients postoperatively compared with preoperative values.ConclusionThe incidence of POCD in elderly patients on the first day after minor surgery is higher than previously reported for seven days after major surgery, and is increased after both propofol and sevoflurane anesthesia, compared with age-matched controls. S-100ß protein and Neuron-Specific Enolase levels were unaffected by anesthetic technique.RésuméObjectifLe dysfonctionnement cognitif postopératoire (DCPO) se manifeste chez 26% des patients âgés, sept jours après une opération non cardiaque majeure. Nous avons évalué l’incidence de DCPO et les modifications des marqueurs sériques d’atteinte neuronale (protéine S- 100ß et énolase neurospécifique), 24 h après une anesthésie à un seul médicament, le propofol ou le sévoflurane, chez des patients âgés qui ont subi une opération mineure.MéthodeLes patients (n = 30, moyenne de 73 ans, limites de 65–86 ans) opérés pour cystoscopie ou hystéroscopie, ont été randomisés à l’insu d’un observateur pour une anesthésie avec propofol ou sévoflurane. Les changements aux tests neuropsychologiques (test Stroop, test modifié de remémoration de mots) ont été notés 24 h après l’opération et comparés à ceux de sujets témoins appariés selon l’âge (n = 15) au moyen de l’analyse de l’écart réduit. On a aussi noté les changements de niveaux de protéines S- 100ß et d’énolase neurospécifique.RésultatsLe DCPO était présent chez 7/15 [47% (intervalle de confiance de 95% (IC) 21 à 72%)] patients qui ont reçu le propofol et chez 7/15 [47%(ICde95% 21 à 72%)] patients qui ont reçu le sévoflurane, comparativement à 1/15 [7% (IC de 95% 6 a 19%)] témoins, P = 0,03. Les niveaux de protéines S- 100ß et d’énolase neurospécifique n’étaient pas significativement différents avant et après l’opération sous anesthésie.ConclusionLe premier jour après une opération mineure, l’incidence de DCPO chez les patients âgés est plus élevée qu’on ne le rapportait auparavant sept jours après une intervention majeure. Elle est augmentée avec le propofol et le sévoflurane, en comparaison avec des témoins du même âge. Les niveaux de protéines S- 100ß et d’énolase neurospécifique ne sont pas modifiés par la technique anesthésique.

The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine

In this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post‐induction. Patients receiving diclofenac had significantly lower pruritus scores at 30 min (p = 0.0076), 2, 4, 8 and 24 h postoperatively, as well as significantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the first 24 h was also significantly lower in this group. In conclusion, rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus. It also significantly reduces pain and further analgesic requirements postoperatively.

Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in paravertebral analgesia for breast surgery

The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra‐ and postoperative paravertebral analgesia. Patients were randomly allocated to four groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus levobupivacaine 0.25% plus fentanyl 50 μg followed by an infusion of levobupivacaine 0.05% with fentanyl 4 μg.ml−1; Group LC received 19 ml bolus levobupivacaine 0.25% plus clonidine 150 μg followed by an infusion of levobupivacaine 0.05% with clonidine 3 μg.ml−1; Group C (control) received general anaesthesia without paravertebral analgesia. All groups received postoperative i.v. morphine patient controlled analgesia (PCA). Although mean (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg] and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p < 0.01, paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension, respectively.

Intrathecal morphine: one year's experience in cardiac surgical patients.

OBJECTIVES This study was designed to assess the benefits and complications associated with the use of intrathecal morphine (ITM) in patients undergoing coronary artery bypass surgery (CABG). DESIGN This was a retrospective chart review. SETTING The study was performed in a single hospital that is affiliated with a university medical school. PARTICIPANTS The charts of all patients who presented for CABG in a 12-month period were reviewed. INTERVENTIONS All patients entered into the study had received ITM (0.03 mg/kg) at induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Complete data were available for 152 patients (86%). Median duration of ventilation postoperatively was 12 hours, and median duration of stay in the ICU was 72 hours. All patients received additional postoperative opioid analgesia, many by the epidural route. Fifteen percent developed respiratory complications, and the incidence of respiratory depression was 1.9%. Thirty-five percent required inotropic support; 17% percent were treated for hypertension; and 49% received antiarrhythmic therapy. The re-infarction rate was 2.6%, and 3% developed cardiac tamponade. Three patients developed neurologic complications unrelated to lumbar puncture. There were no in-hospital deaths. CONCLUSIONS ITM is safe and provides effective pain relief after cardiac surgery. The high incidence of respiratory depression confirms the need for close observation of these patients postoperatively.

An Assessment of the Value of Intraperitoneal Meperidine for Analgesia Postlaparoscopic Tubal Ligation

Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P < 0.01) and with movement (P < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. Implications The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.

Intraperitoneal pethidine versus Intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: Randomized trial

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary end-points were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6±0.8 vs. 2.4±0.9 cm; p<0.001; pain upon movement at 4 hours: 2.1±0.9 vs. 3.1±1.2 cm; p<0.001). The total dose of pethidine administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9±3.9 vs. 55.9±4.4 mg; p<0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.RésuméLa cholécystectomie laparoscopique est réalisée dans le monde entier et peut être réalisée en ambulatoire. Nous avons comparé par une étude randomisée les bénéfices de la pethidine en intraperitoneal comparée à la pethidine en intramusculaire pour l’analgésie postcholecystectomic laparoscopique. Cent patients consécutifs, ASA I ou II, ont été randomisés pour recevoir soit de la pethidine en intra-musculaire (54 patients) ou en intrapéritonéale (46 patients). De la bupivacaïne a été administrée en intrapéritonéale chez tous les patients. Les critères de jugement principaux et secondaires ont été les scores de la douleur et de la nausée à des intervalles successifs post-opératoires. Tous les patients inclus ont complété l’étude. La douleur au repos et lors des mouvements a été significativement moindre dans le groupe recevant de la pethidine en intrapéritonéale à chaque intervalle étudié [douleur au repos à 4 heures: 1.6 (0.8) cm vs. 2.4 (0.9) cm; p=0.001; douleur lors des mouvements à 4 heures: 2.1 (0.9) cm vs. 3.1 (1.2) cm; p=0.001]. La dose totale de pethidine administrée via la PCA pendant les 24 premières heures après chirurgie a également été plus basse dans ce groupe [dose totale 50.9 (3.9) mg vs. 55.9 (4.4) mg; p=0.001]. Il n’y avait aucune différence statistiquement significative en ce qui concernait la fréquence respiratoire quel que soit le moment de l’étude. La pethidine en intrapéritonéale est supérieure à la pethidine en intramusculaire pour l’analgésie de la douleur post-cholécystectomie laparoscopique. Cette amélioration a été accomplie au prix de plus de nausées mais sans augmentation significative des vomissements. L’utilisation de cette route d’administration a des implications importantes chez le patient opéré sous laparoscopic, en particulier, vu la tendance actuelle à élargir les indications de la chirurgie ambulatoire.ResumenLa colecistectomía laparoscópica es el procedimiento más empleado en cirugía ambulatoria. Efectuamos un estudio comparative aleatorio sobre los efectos, de la petidina intraperitoneal vs intramuscular, en la analgesia postcolecistectomía laparoscópica. 100 pacientes ASA I o II fueron aleatoriamente distribuidos en 2 grupos: petidina intramuscular (n=54) y petidina intraperitoneal (n=46); a este último grupo se le asoció bupivacaina intraperitoneal. Se investigaron el dolor y las nauseas durante el postoperatorio. Todos los pacientes completaron el estudio. El dolor postoperatorio tanto en reposo como con la movilización fue significativamente menor en el grupo de petidina intraperitoneal [dolor en reposo a las 4 horas 1.6 (0.8) cm vs 2.4 (0.9) cm; p<0.001; dolor a la movilización a las 4 horas 2.1 (0.9) cm vs 3.1 (1.2) cm; p<0.001]. Además, en este grupo la dosis total de petidina administrada en las primeras 24 horas del periodo postoperatorio fue menor [dosis total 50.9 (3.9) mg vs 55.9 (4.4) mg, p<0.001]. No se observaron diferencias significativas en la frecuencia respiratoria a lo largo del periodo postoperatorio. La analgesia proporcionada por la administración intraperitoneal de petidina es superior a la obtenida por inyección intramuscular, aunque se produzcan más nauseas pero sin que se incremente la frecuencia de vómitos. Dada la accesibilidad de esta vía para la administración de analgésicos este proceder debe tenerse muy en cuenta en las técnicas laparoscópicas, especialmente si se quiere incrementar la realización de las mismas de manera ambulatoria.