Marc De Kock

Patient-Controlled Analgesia in the Management of Postoperative Pain

Patient-controlled analgesia (PCA) is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain. Since its introduction in the early 1980s, the daily management of postoperative pain has been extensively optimised. The use of PCA in hospitals has been increasing because of its proven advantages over conventional intramuscular injections. These include improved pain relief, greater patient satisfaction, less sedation and fewer postoperative complications.All PCA modes contain the following variables: initial loading dose, demand dose, lockout interval, background infusion rate and 1-hour or 4-hour limits. Morphine is the most studied and most commonly used intravenous drug for PCA. In spite of the fact that it is the ‘first choice’ for PCA, other opioids have been successfully used for this option.The most observed adverse effects of opioid-based PCA are nausea and vomiting, pruritis, respiratory depression, sedation, confusion and urinary retention.Although intravenous PCA is the most studied route of PCA, alternative routes have extensively been described in the literature. PCA by means of peridural catheters and peripheral nerve catheters are the most studied. Recently, transdermal PCA has been described. The use of peripheral or neuraxial nerve blocks is recommended to avoid the so called opioid tolerance observed with the intravenous administration of opioids.Numerous studies have shown the superiority of epidural PCA to intravenous PCA. The beneficial postoperative effects of epidural analgesia are more apparent for high-risk patients or those undergoing higher risk procedures. PCA with peripheral nerve catheters results in increased postoperative analgesia and satisfaction for surgery on upper and lower extremities. Serious complications occur rarely with these catheters.With the introduction of an Acute Pain Service, management of postoperative pain can be improved. This will also help to minimise adverse effects related to PCA and to avoid lethal mishaps.

Neutrophil:Lymphocyte Ratio and Intraoperative Use of Ketorolac or Diclofenac are Prognostic Factors in Different Cohorts of Patients Undergoing Breast, Lung, and Kidney Cancer Surgery

BackgroundInflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries.MethodsWe performed an observational study in early breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and multivariate analyses (Cox model).ResultsIn breast cancer (Centre 1), NLRxa0≥xa04 is associated with a higher risk of relapse (hazards ratio (HR)xa0=xa02.41; 95xa0% confidence interval (CI) 1.01–5.76; Pxa0=xa00.048). In breast cancer (Centre 2), NLRxa0≥xa03 is associated with a higher risk of relapse (HRxa0=xa04.6; 95xa0% CI 1.09–19.1; Pxa0=xa00.04) and higher mortality (HRxa0=xa04.0; 95xa0% CI 1.12–14.3; Pxa0=xa00.03). In kidney cancer, NLRxa0≥xa05 is associated with a higher risk of relapse (HRxa0=xa01.63; 95xa0% CI 1.00–2.66; Pxa0=xa00.05) and higher mortality (HRxa0=xa01.67; 95xa0% CI 1.0–2.81; Pxa0=xa00.05). In lung cancer, NLRxa0≥xa05 is associated with higher mortality (HRxa0=xa01.45; 95xa0% CI 1.02–2.06; Pxa0=xa00.04). The intraoperative use of NSAIDs in breast cancer patients (Centre 1) is associated with a reduced recurrence rate (HRxa0=xa00.17; 95xa0% CI 0.04–0.43; Pxa0=xa00.0002) and a lower mortality (HRxa0=xa00.25; 95xa0% CI 1.08–0.75; Pxa0=xa00.01). NSAIDs use at the beginning of the surgery is independently associated with a lower metastases risk after lung cancer surgery (HRxa0=xa00.16; 95xa0% CI 0.04–0.63; Pxa0=xa00.009). Ketorolac use is independently associated with longer survival (HRxa0=xa00.55; 95xa0% CI 0.31–0.95; Pxa0=xa00.03).ConclusionsIn these cohorts, these analyses show that NLR is a strong perioperative prognosis factor for breast, lung, and kidney cancers. In this context, intraoperative NSAIDs administration could be associated with a better outcome.

Something new about ketamine for pediatric anesthesia

Purpose of review This review discusses the place of the old anesthetic ketamine in pediatric anesthesia. Recent findings Despite the availability of modern alternatives, ketamine remains a frequently used drug particularly for anesthesia in high-risk children and for procedures outside the operating room. In adult patients undergoing surgery, a renewed interest in this drug is noted. It is the consequence of recent demonstrations of the following effects. First, ketamine is highly effective against surgery and opiate-induced hyperalgesia. Second, it has original antiproinflammatory properties. In other words, it promotes self-limitation of the inflammatory response that follows surgery. In the pediatric population, these benefits wait to be confirmed. Finally, questions arise about the safety of ketamine anesthesia. Ketamine is a potent proapoptotic drug. In rodents treated during the critical period for central nervous system development, long-term behavioral deficits were noted after an anesthetic dose of ketamine. The exact consequences of these proapoptotic properties on human brain tissue development have to be exactly determined and are still debatable. Summary Ketamine has not yet revealed all its interactions in humans. Recent discoveries indicate interesting properties on the one hand and potentially deleterious effects on the other.

alpha(2)-adrenoceptor agonists and stress-induced analgesia in rats: Influence of stressors and methods of analysis

The present experiments were de signed to investigate the role of housing and handling conditions during testing, as well as data analysis, on the outcome of antinociceptive testing of alpha(2)-adrenoceptor agonists, fentanyl, and a high dose of chlordiazepoxide in the tail withdrawal reaction test (TWR test) in rats. Dose-response curve data were obtained with fentanyl, clonidine, xylazine, dexmedetomidine, and 40.00 mg/kg chlordiazepoxide and were compared under normal TWR test conditions and during immobilization or immobilization with continuous painful stimulation. Data were analyzed in terms of ah-or-none criteria as well as percentage maximum possible effect (%MPE) analysis over the total measurement period or at any specific time point during testing. The results indicate that stress, induced by immobilization and immobilization with long-term-applied paw pressure, unmasked possible antinociceptive properties of the various alpha(2)-adrenoceptor agonists and potentiated the effects of fentanyl. Stress also unmasked the positive effects of benzodiazepines. The manner of data analysis was shown to significantly affect the outcome measured in stress and nonstress conditions. The MPE analysis, particularly at one time point, appeared much more sensitive than the ah-or-none criteria. The data indicate that the housing and handling conditions of animals during testing, together with data analysis, may affect the outcome of different classes of compounds in the TWR test, and this knowledge may help control for false positive results

Is the Neutrophil-to-Lymphocyte Ratio more correlated than C-reactive protein with postoperative complications after major abdominal surgery?

Background. The Neutrophil-to-Lymphocyte Ratio (NLR) is an inflammatory marker that has proven usefulness for predicting late complications. Whether it is associated with immediate postoperative complications after abdominal surgery is not known. In this study, we attempted to correlate the NLR and the C-reactive protein (CRP) with postoperative complications rate. Methods. We performed a post-hoc analysis of previously collected data concerning 82 consecutive patients (median age: 62 years, range: 27–80, female/male 32/50) undergoing major abdominal surgeries. For each patient, we recorded preoperative characteristics, the NLR and CRP values, and postoperative complications (between D + 8 and D + 30) such as infections (N = 29), cardiovascular complications (N = 12) and other complications (N = 28). We performed uni- and multivariate analyses using logistic/linear regression models. Results. Patients with complications did not present a higher preoperative NLR than those without, but a higher ratio at D + 7 (10.73 ± 9.86 vs. 4.73 ± 3.38 without complication) (P < 0.001). In the univariate analysis, the NLR at D + 7 was associated with postoperative complications (P < 0.001). At D + 7, in the multivariate analysis, an increased NLR was associated with more complications (P < 0.001), whereas none of the other factors, including CRP, showed any correlation. Conclusion. Postoperative NLR at day 7 after major abdominal surgery is associated with complications during the first postsurgical month, in contrast with the CRP level. The NLR is a simple and interesting parameter in the perioperative period.

Inflammation-based scores: a new method for patient-targeted strategies and improved perioperative outcome in cancer patients.

Systemic inflammatory response (SIR) has actually been shown as an important prognostic factor associated with lower postoperative survival in several types of cancer. Thus, the challenge for physicians is to find specific, low-cost, and highlyreliable inflammatory markers, clearly correlated with prognosis and able to preoperatively stratify patients risk. Inflammation is a promising target to improve perioperative outcome, and data show that anti-inflammation techniques have a great potential in the perioperative period of cancer surgery. Inflammation scores could be useful to stratify patients with a potential better response to anti-inflammation strategies. Furthermore, inflammation scores could prevent failure of clinical trials by a better definition of patients to be included in such trials; inflammation scoring could clarify the real role of different drugs and techniques on outcome after cancer surgery, defining if different therapies are required for different patients. The role of this review is to focus on the currently available scores, in order to clarify their rationale and to analyze the actual evidence and limits, providing physicians with an updated overview of the possible inflammation-based prognostic scores for cancer patients undergoing surgery.

What is the normal value of the neutrophil-to-lymphocyte ratio?

BackgroundNeutrophil-to-lymphocyte ratio (NLR) has proven its prognostic value in cardiovascular diseases, infections, inflammatory diseases and in several types of cancers. However, no cut-off has been proposed on the basis of reference values coming from healthy population.MethodsRoutine blood samples were obtained (nxa0=xa0413) from workers (age: median 38, range: 21–66xa0years) involved in a health care prevention program, to determine means, standard deviations (SDs), 95% confidence intervals (95% CI), percentiles P2.5 and P97.5. A second independent sample of healthy volunteers is compared (nxa0=xa029).ResultsThe mean NLR is 1.65 [±1.96 SD: 0.78–3.53] (95% CI [0.75–0.81] and [3.40–3.66]). In the second cohort (healthy control), the NLR values are in the same range, whichever the used analyzer. No NLR assessed in the validation series is out of the proposed limits.ConclusionsWe have identified that the normal NLR values in an adult, non-geriatric, population in good health are between 0.78 and 3.53. These data will help to define the normal values of the NLR.

An improved porcine model of stable methacholine-induced bronchospasm

AbstractnObjective. To validate an animal model replicating the pathophysiological characteristics of severe induced bronchospasm observed in humans, with a high level of stability permitting measurements such as the assessment of ventilation-perfusion relationships with the multiple inert gas elimination technique.nDesign and setting. Experimental study in an animal research laboratory.nSubjects. 13 piglets (age 3–4xa0months) were studied and 7 underwent the complete protocolnInterventions. The animals were anesthetized and paralyzed. Mechanical ventilation was initiated in a volume-controlled mode. Ventilatory parameters were adjusted to obtain normocapnia and were maintained constant during the bronchospasm. Methacholine was administered via a synchronized nebulizer and progressively adjusted to obtain a stable twofold increase in peak inspiratory pressure.nMeasurements and results. Cardiopulmonary physiological data including assessment of lung mechanics and measurement of ventilation-perfusion relationships were obtained before and during the bronchospasm. Peak inspiratory pressure increased from 19.7±2.9 to 44.4±7.1xa0cmH2O during the bronchospasm. The latter remained stable over 2xa0h. Respiratory mechanics, gas exchange, and ventilation-perfusion distribution changes typical of those observed in severe bronchospasm in humans were observed in all animals.nConclusions. The present experimental model replicates some of the physiopathological characteristics of severe human bronchospasm, and its stability should facilitate studies of the effects of different ventilatory modes in the setting of acute severe asthma.

Perspectives in anaesthesia for cancer surgery

BackgroundIt is a fact that inflammatory scores are important prognostic factors in cancer surgery. Many data have been published last year showing that inflammation is a causative event in many cancers and a concomitant event in all malignant tumours. Monitoring of the inflammationWhat is new is that we can assess inflammatory status during the preoperative period of our cancer patients with simple and widely available parameters, such as the neutrophil/lymphocyte ratio. This kind of biomarkers will be helpful, for the clinicians, to stratify the patients and, for the researcher, to incorporate it in clinical trials.Rationale for trials after database analysesPromising clinical trials, focusing on perioperative inflammation, are ongoing. Rationale for these trials came from database analyses. This kind of analyses must be extended to follow the long-term effects of our interventions. Non-steroidal anti-inflammatory drugsWe have shown a correlation between non-steroidal anti-inflammatory drugs, especially ketorolac, and improved outcome (metastasis-free survival and/or overall survival) in breast and lung cancer patients. ConclusionFocusing on a high-risk group with preoperative inflammation could lead to a clinical trial to test the effect of ketorolac on cancer outcome.

Does the perioperative analgesic/anesthetic regimen influence the prevalence of long-term chronic pain after mastectomy?

STUDY OBJECTIVEnTo investigate if the anesthetic/analgesic regimen is associated with the risk of reporting long-term chronic postmastectomy pain (CPMP).nnnDESIGNnCross-sectional surveynnnSETTINGnAcademic hospitalnnnPATIENTSnA total of 267 women having undergone mastectomy with axillary lymph node dissection between 2003 and 2008 INTERVENTIONS: All patients were contacted between October and December 2012, with a questionnaire asking for persistent pain after surgery and its characteristics.nnnMEASUREMENTSnBesides demographical data, tumor characteristics, and adjuvant treatment, we recorded type and doses of intraoperative anesthetics/analgesics (sufentanil, ketamine, clonidine, nonsteroidal anti-inflammatory drugs, MgSO4, propofol, or halogenated agents).nnnRESULTSnOf the 128 patients returning analyzable questionnaires, 43.8% reported chronic pain (48.2% with neuropathic characteristics). Multivariate logistic/linear regression model showed 4 factors independently associated with persistent pain: recall of preoperative pain (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.09-1.48), chemotherapy (OR, 1.32; 95% CI, 1.13-1.55), need for strong opioids in postanesthesia care unit (OR, 1.30; 95% CI, 1.11-1.53), and halogenated agent anesthesia (OR, 0.81; 95% CI, 0.70-0.95).nnnCONCLUSIONnIn conclusion, our study confirms the high prevalence of CPMP, 4 to 9 years after surgery. Recall of preoperative pain, chemotherapy, and need for strong opioids in the postanesthesia care unit were all associated with the presence of chronic pain. Of the intraoperative analgesics/anesthetics studied, only use of halogenated agents was associated with a lower prevalence of CPMP.