Pascal Alfonsi

Nefopam and Ketamine Comparably Enhance Postoperative Analgesia

Opioids alone sometimes provide insufficient postoperative analgesia. Coadministration of drugs may reduce opioid use and improve opioid efficacy. We therefore tested the hypothesis that the administration of ketamine or nefopam to postoperative patients with pain only partly alleviated by morphine reduces the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n = 77) recovering from major surgery were given up to 9 mg of IV morphine. Those who still had pain were randomly assigned to blinded administration of 1) isotonic saline (control group; n = 21), 2) ketamine 10 mg (ketamine group; n = 22), or 3) nefopam 20 mg (nefopam group; n = 22). Three-milligram morphine boluses were subsequently given at 5-min intervals until adequate analgesia was obtained, until 60 min elapsed after the beginning of study drug administration, or until ventilation became insufficient (respiratory rate <10 breaths/min or saturation by pulse oximetry <95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly more in the control group (mean ± sd; 17 ± 10 mg) than in the nefopam (10 ± 5 mg; P < 0.005) or ketamine (9 ± 5 mg; P < 0.001) groups. Morphine titration was successful in all ketamine and nefopam patients but failed in four control patients (two because of respiratory toxicity and two because of persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam, and sedation was more intense with ketamine; however, the incidence of other potential complications did not differ among groups.

Nefopam, a Nonsedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold in Unanesthetized Subjects

BackgroundThe analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering. MethodsNine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34°C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response. ResultsNefopam did not significantly modify the slopes for sweating (0.0 ± 4.9°C · &mgr;g−1 · ml; r2 = 0.73 ± 0.32) or vasoconstriction (−3.6 ± 5.0°C · &mgr;g−1 · ml; r2 = −0.47 ± 0.41). In contrast, nefopam significantly reduced the slope of shivering (−16.8 ± 9.3°C · &mgr;g−1 · ml; r2 = 0.92 ± 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 ± 0.4°C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds. ConclusionsMost drugs with thermoregulatory actions—including anesthetics, sedatives, and opioids—synchronously reduce the vasoconstriction and shivering thresholds. However, nefopam reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulations of vasoconstriction and shivering can be separated is of clinical and physiologic interest.

Cardiac function during intraperitoneal CO2 insufflation for aortic surgery : A transesophageal echocardiographic study

The effect of laparoscopy on cardiac function is controversial. We hypothesized that cardiac dysfunction related to increased afterload could be predominant in patients undergoing elective abdominal aortic repair. To test this hypothesis, we conducted a transesophageal echocardiographic study in 15 patients during laparoscopic aortic surgery. We systematically assessed left ventricular (LV) and right ventricular (RV) functions. Measurements were obtained in the supine position without pneumoperitoneum and with an intraabdominal pressure of 14 mm Hg. Then, patients were turned to the right lateral position without pneumoperitoneum and intraabdominal pressure was increased to 7 mm Hg and to 14 mm Hg. Pneumoperitoneum induced a 25% arterial blood pressure increase and a 38% increase in LV systolic wall stress. A 25% decrease in LV ejection fraction and an 18% decrease in LV stroke volume were observed, associated with an increase in LV end-systolic volume. LV diastolic function impairment was observed without change in LV end-diastolic volume. Respiratory alterations in superior vena cava diameter were never observed, suggesting that volume status remained optimal. Respiratory changes in RV stroke volume were increased according to intraabdominal pressure and body position, reflecting an increase in RV afterload. In conclusion, peritoneal CO2 insufflation in patients scheduled for laparoscopic aortic surgery could impair LV and RV systolic functions as a consequence of increased afterload.

Total Laparoscopic Aortobifemoral Bypass: Short- and Middle-Term Results

We describe early and mid-term results of total laparoscopic aortofemoral bypass (TLAFB). TLAFB was performed in 150 cases of severe aortoiliac occlusive disease. Aortic approaches included transperitoneal left retrocolic (n = 86), left retrorenal (n = 51), and direct (n = 4); the retroperitoneoscopic approach was used in nine cases. The procedure was totally laparoscopic in 145 patients (96.6%). Median operative and clamping times were 260 (120-450) and 81 (36-190) min, respectively. Thirty-day mortality was 2.7%. Nonlethal systemic, local vascular, and local nonvascular complications occurred in 21 (14.3%), seven (4.8%), and two (1.3%) patients, respectively. Median return to general diet and ambulation were, respectively, days 2 and 3. Median hospital stay was 7 days. Follow-up was 25.2 +/- 17.6 months (range 1-60) with 3-year primary and secondary actuarial patency rates of 93% and 95.6%, respectively. TLAFB gives early and mid-term patency rates comparable to open direct repair. Laparoscopy allows faster recovery and reduces operative trauma.

Nefopam and alfentanil additively reduce the shivering threshold in humans whereas nefopam and clonidine do not.

Background:Induction of therapeutic hypothermia is often complicated by shivering. Nefopam reduces the shivering threshold with minimal side effects. Consequently, nefopam is an attractive component for induction of therapeutic hypothermia. However, nefopam alone is insufficient; it will thus need to be combined with another drug. Clonidine and alfentanil each reduce the shivering threshold. This study, therefore, tested the hypothesis that nefopam, combined either with clonidine or alfentanil, synergistically reduces the shivering threshold. Methods:For each combination, ten volunteers were studied on 4 days. Combination 1: (1) control (no drug); (2) nefopam (100 ng/ml); (3) clonidine (2.5 &mgr;g/kg); and (4) nefopam plus clonidine (100 ng/ml and 2.5 &mgr;g/kg, respectively). Combination 2: (1) control (no drug); (2) nefopam (100 ng/ml); (3) alfentanil (150 ng/ml); and (4) nefopam plus alfentanil (100 ng/ml and 150 ng/ml, respectively). Lactated Ringer’s solution (approximately 4°C) was infused to decrease core temperature. Mean skin temperature was maintained at 31°C. The core temperature that increased oxygen consumption to more than 25% of baseline identified the shivering threshold. Results:With nefopam and clonidine, the shivering thresholds were significantly lower than on the control day. The shivering threshold decreased significantly less than would be expected on the basis of the individual effects of each drug (P = 0.034). In contrast, the interaction between nefopam and alfentanil on shivering was additive, meaning that the combination reduced the shivering threshold as much as would be expected by the individual effect of each drug. Conclusions:Nefopam and alfentanil additively reduce the shivering threshold, but nefopam and clonidine do not.

Laparoscopic abdominal aortic aneurysm repair in octogenarians

OBJECTIVE Open abdominal aortic aneurysm (AAA) repair in octogenarians is considered to have higher risks of mortality and systemic complications compared with younger patients. The purpose of our work is to present our experience with total laparoscopic repair for AAA in this subset of patients. METHODS From February 2002 to February 2008, 29 octogenarian patients underwent total laparoscopic AAA repair. Median age was 82 years (range, 80-85 years). Median aneurysm size was 52 mm (range, 40-85 mm). Disease was classified as American Society of Anesthesiologist (ASA) class II in 12 patients and class III in 17 patients. Ten patients presented with past medical history of myocardial infarct (34.5%). RESULTS We implanted 12 tube grafts and 17 bifurcated grafts. Twenty-six procedures were totally laparoscopic (89.6 %). Median operative time and aortic clamping time were 280 min (range, 160-480 min) and 75 min (range, 22-125 min), respectively. Two patients with juxtarenal AAA underwent suprarenal clamping. Median blood loss was 1100 cc (range, 600-3000 cc). Four patients (13.8%) needed adjunctive vascular procedures because of intraoperative complications. Two patients died in the postoperative course (6.9%). Four patients developed severe systemic non-lethal complications (14.8%, pneumopathies). Mild or moderate systemic complications were observed in 14 patients (51.8%) including transient renal insufficiencies without dialysis (13) and cardiac arrhythmia (1). Postoperative creatinine levels returned to baseline before discharge in all patients. Liquid diet was reintroduced after a median duration of 2 days (range, 1-10 days) and most patients were ambulatory by day four (range, 3-30 days). Median stays in intensive care unit and hospital were 72 hours (range, 12-1368 hours) and 11 days (range, 6-74 days), respectively. Sixteen patients (59.2%) were discharged directly to home with complete recovery. After a median follow-up of 24 months (range, 2-48 months), 23 patients are still alive and regained their baseline status. Four patients died after hospital discharge of non-vascular etiologies. CONCLUSION Total laparoscopic AAA repair is a worthwhile but challenging procedure in octogenarians. Laparoscopy is complementary to open surgery and EVAR in this subset. These results encourage us to offer laparoscopic AAA repair in good surgical risk octogenarians.

Totally laparoscopic tube graft bypass for infrarenal aortic aneurysm : a well-established surgical technique

Abstract Abdominal aortic aneurysm (AAA) repair enters the field of laparoscopic surgery. Main advantage of laparoscopic AAA repair is to perform the gold standard endoaneurysmorraphy with a reduced surgical trauma. Since 2001, the technique has evolved and is now well-established. We describe the standard technique of totally laparoscopic endoaneurysmorraphy with tube graft interposition through a transperitoneal left retrorenal approach. Main technical points are discussed.

Mild hypothermia does not increase bacterial proliferation on implanted vascular grafts

BACKGROUND Mild hypothermia may offer protection against spinal cord ischemia during aortic surgery. However, hypothermia also promotes postoperative infection via two mechanisms: peripheral vasoconstriction and impairment of various immune functions. If mild hypothermia aggravates graft infections, immune function impairment would presumably be the most important factor because thermoregulatory vasoconstriction does not appreciably reduce aortic blood flow. We therefore tested the hypothesis that resistance to vascular graft infection is not reduced by mild perioperative hypothermia in dogs. METHODS After colonization with a solution of Staphylococcus epidermidis, prostheses were used to replace the infrarenal aorta in 20 dogs. During surgery, the dogs were randomly assigned to maintain of normothermia or passive cooling. Seven days later, grafts were recovered for bacteriologic study. RESULTS Colony counts for the grafts removed from the normothermic and hypothermic dogs did not differ significantly. CONCLUSIONS Mild perioperative hypothermia does not increase proliferation of S epidermidis on aortic vascular grafts.