Preoperative Paravertebral Block and Chronic Pain after Breast Cancer Surgery: A Double-blind Randomized Trial.

BACKGROUND: The effectiveness of paravertebral block in preventing chronic pain after breast surgery remains controversial. The primary hypothesis of this study was that paravertebral block reduces the incidence of chronic pain 3 months after breast cancer surgery. METHODS: In this prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, 380 women undergoing partial or complete mastectomy with or without lymph node dissection were randomized to receive preoperative paravertebral block with either 0.35 ml/kg 0.75% ropivacaine (paravertebral group) or saline (control group). Systemic multimodal analgesia was administered in both groups. The primary endpoint was the incidence of chronic pain with a visual analogue scale (VAS) score greater than or equal to 3 out of 10, 3 months after surgery. The secondary outcomes were acute pain, analgesic consumption, nausea and vomiting, chronic pain at 6 and 12 months, neuropathic pain, pain interference, anxiety, and depression. RESULTS: Overall, 178 patients received ropivacaine, and 174 received saline. At 3 months, chronic pain was reported in 93 of 178 (52.2%) and 83 of 174 (47.7%) patients in the paravertebral and control groups, respectively (odds ratio, 1.20 [95% CI, 0.79 to 1.82], P = 0.394). At 6 and 12 months, chronic pain occurred in 104 of 178 (58.4%) versus 79 of 174 (45.4%) and 105 of 178 (59.0%) versus 93 of 174 (53.4%) patients in the paravertebral and control groups, respectively. Greater acute postoperative pain was observed in the control group 0 to 2 h (area under the receiver operating characteristics curve at rest, 4.3 ± 2.8 vs. 2.9 ± 2.8 VAS score units × hours, P < 0.001) and when maximal in this interval (3.8 ± 2.1 vs. 2.5 ± 2.5, P < 0.001) but not during any other interval. Postoperative morphine use was 73% less in the paravertebral group (odds ratio, 0.272 [95% CI, 0.171 to 0.429]; P < 0.001). CONCLUSIONS: Paravertebral block did not reduce the incidence of chronic pain after breast surgery. Paravertebral block did result in less immediate postoperative pain, but there were no other significant differences in postoperative outcomes.

Postoperative pain scores and opioid consumption in opioid-dependent patients with cancer after intraoperative remifentanil analgesia: A prospective case-controlled study.

BACKGROUND: Opioid dependency is becoming increasingly common among surgical patients with cancer, and can lead to inadequate pain relief during the initial postoperative period. No guidelines are currently available for the management of perioperative and postoperative morphine administration in these patients. As a first approach, the authors assessed the opioid requirements of these patients during the early postoperative period. METHODS: A group of 35 consecutive surgical patients with cancer on opioid therapy (opioid-dependent group) for cancer pain were compared to a matched group of 44 surgical opioid-naive patients (control group). All patients underwent major head and neck or abdominal surgery. The following parameters were recorded and compared: preoperative and postoperative morphine consumption, patient-controlled analgesia records and Visual Analog Scale scores, intraoperative remifentanil and desflurane consumption, Bispectral Index monitoring values, heart rate, and blood pressure. RESULTS: Remifentanil requirements were significantly higher (1.4-fold) in the opioid-dependent group compared to the control group (p < 0.05). On postoperative day 1, morphine requirements were significantly higher in the opioid-dependent group (2.3-fold) compared to the control group (p < 0.05). Baseline heart rate was significantly higher in the opioid-dependent group and this difference remained significant during surgery, no significant difference in blood pressure was observed between the two groups. CONCLUSION: This study shows a 40 percent increase of intraoperative remifentanil requirements in opioid-dependent patients during cancer surgery. Morphine requirements during the postoperative period were increased by up to 140 percent.

Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective Observational Feasibility Study.

BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB. METHODS: This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB. TPVB was performed before surgery under ultrasound guidance with 20 mL of 0.75% ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the anterior chest wall. The PDR was defined as the maximal increase in pupil diameter after a standardized noxious stimulus, expressed as a percentage of the initial pupil diameter. The PDR was recorded twice in the same eye for each patient after a stimulus on both the TPVB and the control sides. Postoperative pain scores were recorded in a postanesthesia care unit. The primary outcome was the difference between the PDR on the TPVB and the control sides. RESULTS: The median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%-66%) on the control side. There was a significant difference in the PDR between the TPVB and the control sides with a Hodges-Lehmann estimate of absolute difference of 37% points (95% confidence interval, 25-52, P < .001). Median postoperative pain scores (interquartile range) in the postanesthesia care unit were 1 (0-3) at rest and 1 (0-3) during mobilization, respectively. There was a linear correlation between maximal postoperative pain scores and the PDR on the TPVB side with a Pearson's correlation coefficient r = 0.40 (95% confidence interval, 0.06-0.66, P = .02). No correlation was found between the number of blocked dermatomes and maximal postoperative pain scores (P = .06) or between the number of blocked dermatomes and the PDR on the TPVB side (P = .15). CONCLUSIONS: This proof-of-concept trial suggests that the effect of TPVB could be monitored by measuring the PDR after anterior chest wall stimulation in the dermatome of interest.

Contribution of Low-Dose Computerized Tomography With Digital Multiplanar Reconstructions in Thoracic Epidurography and Correlation With Sensory Block in Postoperative Analgesia.

BACKGROUND: The level of sensory block in postoperative epidural analgesia has been correlated with conventional contrast epidurography in only one study, while low-dose CT scan epidurography with multiplanar reconstruction may be a better tool for this purpose. OBJECTIVES: The primary objective of this study was to evaluate, by CT imaging and digital multiplanar reconstruction, the spread and distribution of contrast medium injected into the epidural space through a catheter inserted in a low thoracic position for postoperative analgesia. MATERIALS AND METHODS: Ten patients undergoing major abdominal cancer surgery with effective epidural analgesia were prospectively included at postoperative day three. Two consecutive boluses of 5 mL of a mixture of ropivacaine and contrast medium were injected at 15 minutes intervals into the epidural space. Multislice low-dose CT scan epidurography and an assessment of the sensory block were performed before and after injection of the second bolus. The primary objective was to assess the contribution of CT scan epidurography to predict a correlation between the level of sensory block and the spread of the contrast medium in the epidural space; the secondary objective was to determine the agreement between the two methods. RESULTS: The spread of contrast material and the clinical sensory block significantly increased after the second injection (32%; P < 0.05). However, no highly significant correlation was observed between the two methods. A gap of two spinal segments of CT opacification was observed in two patients and was confirmed by clinical assessment. CONCLUSIONS: CT epidurography is not closely correlated with a clinical assessment of epidural block; thus, a clinical assessment of the sensory block is mandatory. The use of opioid analgesia in combination with local anesthetics may compensate for the lack of efficacy of local anesthetics alone.

Effect of Alexithymia and Emotional Repression on Postsurgical Pain in Women With Breast Cancer: A Prospective Longitudinal 12-Month Study.

UNLABELLED: Alexithymia, the inability to identify and express emotions, and emotional repression, a defensive mechanism used to avoid unpleasant emotional experience, have been associated with chronic pain and medical illness including breast cancer, but whether these constructs might predict pain after breast cancer surgery has not been assessed. The present study was conducted to assess the predictive value of alexithymia and emotional repression in postoperative pain. Anxiety, depression, catastrophizing, and psychological adjustment were also assessed. Data were collected before surgery, and then at 2 days and 2, 3, 6, and 12 months after surgery. We included 100 pain-free women, 96% of whom were followed for up to 12 months. Separate multivariate analyses identified anxiety as a significant predictor of postsurgical pain at 3 months, alexithymia at 3, 6, and 12 months, and body image and catastrophizing predicted acute or subacute pain at 2 months. In contrast, emotional repression was not predictive of pain. The generalized estimating equation approach was used and identified alexithymia as the only significant predictor of pain during the 12-month period after surgery. Alexithymia, but not emotional repression, predicted the development of persistent pain after breast surgery independently of anxiety and depression. Thus, alexithymia might be involved in mechanisms of pain chronicity. PERSPECTIVE: This prospective study, conducted in women with breast cancer surgery, showed that alexithymia but not emotional repression predicted postsurgical pain. These results highlight the role of dysfunction in emotional processing in the development of postsurgical pain.

Does cognitive functioning predict chronic pain? Results from a prospective surgical cohort.

It is well established that chronic pain impairs cognition, particularly memory, attention and mental flexibility. Overlaps have been found between the brain regions involved in pain modulation and cognition, including in particular the prefrontal cortex and the anterior cingulate cortex, which are involved in executive function, attention and memory. However, whether cognitive function may predict chronic pain has not been investigated. We addressed this question in surgical patients, because such patients can be followed prospectively and may have no pain before surgery. In this prospective longitudinal study, we investigated the links between executive function, visual memory and attention, as assessed by clinical measurements and the development of chronic pain, its severity and neuropathic symptoms (based on the 'Douleur Neuropathique 4' questionnaire), 6 and 12 months after surgery (total knee arthroplasty for osteoarthritis or breast surgery for cancer). Neuropsychological tests included the Trail-Making Test A and B, and the Rey-Osterrieth Complex Figure copy and immediate recall, which assess cognitive flexibility, visuospatial processing and visual memory. Anxiety, depression and coping strategies were also evaluated. In total, we investigated 189 patients before surgery: 96% were re-evaluated at 6 months, and 88% at 12 months. Multivariate logistic regression (stepwise selection) for the total group of patients indicated that the presence of clinical meaningful pain at 6 and 12 months (pain intensity ≥ 3/10) was predicted by poorer cognitive performance in the Trail Making Test B (P = 0.0009 and 0.02 for pain at 6 and 12 months, respectively), Rey-Osterrieth Complex Figure copy (P = 0.015 and 0.006 for pain at 6 and 12 months, respectively) and recall (P = 0.016 for pain at 12 months), independently of affective variables. Linear regression analyses indicated that impaired scores on these tests predicted pain intensity (P < 0.01) and neuropathic symptoms in patients with pain (P < 0.05), although the strength of the association was less robust for neuropathic symptoms. These results were not affected by the type of surgery or presurgical pain, similar findings being obtained specifically for patients who initially had no pain. In conclusion, these findings support, for the first time, the notion that premorbid limited cognitive flexibility and memory capacities may be linked to the mechanisms of pain chronicity and probably also to its neuropathic quality. This may imply that patients with deficits in executive functioning or memory because of cerebral conditions have a greater risk of pain chronicity after a painful event.

Are psychological predictors of chronic postsurgical pain dependent on the surgical model? A comparison of total knee arthroplasty and breast surgery for cancer.

UNLABELLED: Anxiety, depression, and catastrophizing are generally considered to be predictive of chronic postoperative pain, but this may not be the case after all types of surgery, raising the possibility that the results depend on the surgical model. We assessed the predictive value of these factors for chronic postsurgical pain in 2 different surgical models: total knee arthroplasty for osteoarthritis (89 patients, 65% women, age = 69 ± 9 years, baseline pain intensity = 4.7 ± 2.1) and breast surgery for cancer (100 patients, 100% women, age = 55 ± 12 years, no preoperative pain). Data were collected before surgery, then 2 days and 3 months after surgery. Anxiety, depression, and catastrophizing were measured with the Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale, respectively. Pain was assessed with the Brief Pain Inventory. Neuropathic pain was detected with the DN4 questionnaire. Multivariate logistic regression analyses for the total knee arthroplasty and breast surgery models considered together indicated that the presence of clinically meaningful chronic pain at 3 months (pain intensity ≥3/10) was predicted independently by age (P = .04), pain intensity on day 2 (P = .009), and state anxiety (P = .001). Linear regression models also showed that pain magnification, one of the dimensions of catastrophizing, independently predicted chronic pain intensity (P = .04). These results were not affected by the surgical model or by the neuropathic characteristics of the pain. Thus, state anxiety and pain magnification seem to constitute psychological risk factors for chronic postsurgical pain relevant in all surgical models. PERSPECTIVE: This prospective study performed in patients with total knee arthroplasty or breast surgery for cancer shows that state anxiety, amplification of pain, and acute postoperative pain independently predict postsurgical pain at 3 months and that this does not depend on the surgical model.

A double-blind randomized trial of wound and intercostal space infiltration with ropivacaine during breast cancer surgery: effects on chronic postoperative pain.

BACKGROUND: The efficacy of local anesthetic wound infiltration for the treatment of acute and chronic postoperative pain is controversial and there are no detailed studies. The primary objective of this study was to evaluate the influence of ropivacaine wound infiltration on chronic pain after breast surgery. METHODS: In this prospective, randomized, double-blind, parallel-group, placebo-controlled study, 236 patients scheduled for breast cancer surgery were randomized (1:1) to receive ropivacaine or placebo infiltration of the wound, the second and third intercostal spaces and the humeral insertion of major pectoralis. Acute pain, analgesic consumption, nausea and vomiting were assessed every 30 min for 2 h in the postanesthesia care unit and every 6 h for 48 h. Chronic pain was evaluated 3 months, 6 months, and 1 yr after surgery by the brief pain inventory, hospital anxiety and depression, and neuropathic pain questionnaires. RESULTS: Ropivacaine wound infiltration significantly decreased immediate postoperative pain for the first 90 min, but did not decrease chronic pain at 3 months (primary endpoint), or at 6 and 12 months postoperatively. At 3 months, the incidence of chronic pain was 33% and 27% (P = 0.37) in the ropivacaine and placebo groups, respectively. During follow-up, brief pain inventory, neuropathic pain, and anxiety increased over time in both groups (P < 0.001) while depression remained stable. No complications occurred. CONCLUSION: This multicenter, prospective study shows that ropivacaine wound infiltration after breast cancer surgery decreased immediate postoperative pain but did not decrease chronic pain at 3, 6, and 12 months postoperatively.

An analysis of postoperative epidural analgesia failure by computed tomography epidurography.

In this prospective study involving 125 patients, we analyzed epidural analgesia failure after major abdominal surgery using computed tomography (CT) epidurographies to compare the incidence of dislodgement of epidural catheters and leakage of solution from the epidural space between two groups of patients: patients with successful or failed epidural analgesia. Our hypothesis was that the incidence of dislodgement and leakage should be low when epidural analgesia is successful. A thoracic epidural catheter was inserted before general anesthesia and secured by subcutaneous tunneling. Bupivacaine (0.25%) was administered during surgery followed by continuous epidural analgesia with 0.125% bupivacaine (10 mL/h) and morphine (0.25 mg/h) for 48 h. Failure was defined as a visual analog scale pain score at rest more than 30 mm and/or interruption of epidural analgesia before 48 h for any reason. When failure was not due to unintentionally withdrawn, kinked catheters or adverse events (n = 11), a CT scan with contrast injection was performed. Control CT scans were also performed in patients with adequate analgesia (i.e., the success group). The incidence of failure was 24.8% (n = 31). CT scans in the failure group (n = 20) showed seven patients with catheters outside the epidural space, nine with normal distribution, one with unilateral spread, and three with leakage of solution outside the epidural space. In the success group, CT scans (n = 19) showed 11 patients with normal distribution, five with unilateral spread, and three with leakage. We conclude that the major cause of epidural analgesia failure was dislodgment of the catheter. CT scans were mostly useful for detecting leakage of injectate, which may be the early phase of dislodgment.

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.

[Analgesic effects of cyclooxygenase 2 inhibitors]. / Effet antalgique des inhibiteurs de la cyclo-oxygénase 2.

Traditional pain management strategies for cancer pain have relied on the use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant analgesics. However, the substantial adverse effects associated with their use has left many patients without dependable options for effective treatment. Recent advances in the understanding of pain and its pathophysiologic mechanisms have led to the development of novel therapeutics. Cyclooxygenase(Cox)-2-specific inhibitors (coxib) have an established efficacy in the treatment of chronic and acute pain comparable to that of traditional NSAIDs without the degree of gastrointestinal complication or the platelets inhibitor effect of traditional NSAIDs. Numerous studies have shown that coxibs are efficacious in the management of chronic and acute pain in various clinical settings including postoperative pain. The superior safety profile of coxibs in conjunction with a comparable efficacy to nonselective NSAIDs supports the use of coxibs in balanced analgesic regimens and provides the potential to incorporate coxibs into the pain management algorithm used to treat cancer pain.

[Analgesic effects of cyclooxygenase 2 inhibitors]. / Effet antalgique des inhibiteurs de la cyclo-oxygénase 2.

Traditional pain management strategies for cancer pain have relied on the use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant analgesics. However, the substantial adverse effects associated with their use has left many patients without dependable options for effective treatment. Recent advances in the understanding of pain and its pathophysiologic mechanisms have led to the development of novel therapeutics. Cyclooxygenase(Cox)-2-specific inhibitors (coxib) have an established efficacy in the treatment of chronic and acute pain comparable to that of traditional NSAIDs without the degree of gastrointestinal complication or the platelets inhibitor effect of traditional NSAIDs. Numerous studies have shown that coxibs are efficacious in the management of chronic and acute pain in various clinical settings including postoperative pain. The superior safety profile of coxibs in conjunction with a comparable efficacy to nonselective NSAIDs supports the use of coxibs in balanced analgesic regimens and provides the potential to incorporate coxibs into the pain management algorithm used to treat cancer pain.

Intrathecal + PCA morphine improves analgesia during the first 24 hr after major abdominal surgery compared to PCA alone.

PURPOSE: To compare, over a 48-hr follow-up period, the analgesia and side-effects of patient controlled iv analgesia (PCA) with morphine alone vs combined intrathecal and PCA morphine (IT+PCA) in patients undergoing major abdominal surgery. METHODS: Sixty adult patients undergoing abdominal surgery for cancer were randomly allocated to receive preoperative IT (0.3 or 0.4 mg) plus postoperative PCA morphine or postoperative PCA morphine alone. Postoperative analgesia was tested at rest and while coughing on a visual analogue pain scale and morphine consumption was recorded. Patients' satisfaction, arterial oxygen saturation, respiratory rate, episodes of nausea, vomiting and pruritus were also noted. RESULTS: Analgesia at rest and while coughing was significantly better in the IT+PCA morphine group (rest: P = 0.01; coughing: P = 0.005) on the first postoperative day only. IT+PCA morphine constantly provided adequate analgesia during this period. Morphine consumption was lower in the IT+PCA morphine group during this period also (IT+PCA: 9 (17) vs PCA: 40 (26); mg of morphine, mean (SD), P = 0.0001). No difference was found in pain relief and morphine consumption between the groups on the second postoperative day. Nausea and vomiting were more frequent with IT+PCA morphine on the first postoperative day. No respiratory depression occurred in either group. Satisfaction was high in both groups. CONCLUSIONS: IT+PCA morphine improves patient comfort constantly during the first postoperative day after major abdominal surgery. However, after the first postoperative day, IT+PCA morphine provides no additional benefit.

Lidocaine induces a reversible decrease in alveolar epithelial fluid clearance in rats.

BACKGROUND: Lidocaine is widely used in patients with acute cardiac disorders and has also been recently implicated as a possible cause of pulmonary edema after liposuction. The objective of this study was to assess the effect of lidocaine on alveolar fluid clearance, the primary mechanism responsible for the resolution of alveolar edema. METHODS: Alveolar fluid clearance was measured in 29 ventilated rats using our well-validated method over 1 h using a 5% albumin solution instilled into the distal air spaces of the lung. Lidocaine was added to the instilled albumin solution (10(-5) M) or administered intravenously at a dose estimated to achieve a clinically relevant plasma concentration of 10(-5) M. Standard agonists and antagonists were used to determine the effect of lidocaine on alveolar fluid clearance. To determine whether lidocaine acted predominantly on the apical or basal surface, we also used QX314, lidocaine n-ethyl bromide quaternary salt, an analog of lidocaine, which is unable to cross the alveolar epithelium. The effect of lidocaine on the apical epithelial sodium channel transfected in Xenopus oocytes was also studied. RESULTS: Alveolar or intravenous lidocaine decreased alveolar fluid clearance by 50%, an effect that was reversible with the beta2 agonist, terbutaline. Lidocaine acted predominantly on the basal surface of the epithelium because n-ethyl bromide quaternary salt decreased alveolar fluid clearance only when it was given intravenously and because lidocaine did not inhibit the apical epithelial sodium channel when expressed in oocytes. CONCLUSIONS: Lidocaine decreased alveolar fluid clearance by 50%, an effect that may have major clinical implications in the care of patients with cardiac disease or during the perioperative period in some patients. Importantly, the effect of lidocaine was completely reversible with beta2-adrenergic therapy.