Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain.

The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain. Prospective randomized trial assessing the individual or combined application of intraperitoneal tramadol (10 mg/kg) and the selective cannabinoid-2 (CB-2) agonist (R,S)-AM1241 (1 mg/kg) applied postsurgical stress stimulus. Pharmacological specificity was established by antagonizing tramadol with naloxone (0.3 mg/kg) and (R,S)-AM1241 with SR144528 (1 mg/kg). Thermal allodynia was assessed by hot plate test 30 (T30), 60 (T60), and 120 (T120) minutes after incision. Blood samples for plasma IL-6 and IL-2 level determination were obtained 2 hours after incision. Data from 42 rats were included in the final analyses. Significant augmentation of thermal threshold was observed at all time points, after administration of either tramadol or (R,S)-AM1241 compared with the control group (P = 0.004 and P = 0.015, respectively). The combination of (R,S)-AM1241 plus tramadol promoted the induced antinociception in an important manner compared with control (P = 0.002) and (R,S)-AM1241 (P = 0.022) groups. Although the antiallodynic effect produced by tramadol was partially reversed by naloxone 30 and 60 minutes after incision (P = 0.028 and P = 0.016, respectively), SR144528 blocked the effects of (R,S)-AM1241 administration in a significant manner (P = 0.001) at all time points. Similarly, naloxone plus SR144528 also blocked the effects of the combination of (R,S)-AM1241 with tramadol at all time points (P = 0.000). IL-6 level in (R,S)-AM1241 plus tramadol group was significantly attenuated compared with control group (P = 0.000). Nevertheless, IL-2 levels remained unchanged in all experimental groups. It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may improve antinociceptive effects and immune responses of cannabinoids, but this effect does not seem to be superior to that of tramadol alone.

Influence of apneic oxygenation on cardiorespiratory system homeostasis.

PURPOSE: The aim of this study was to elucidate the magnitude of variations in oxygenation indices and the pattern of hemodynamic changes in response to the net effect of tracheal apneic oxygenation (AO) with a view to define the safe time limit of its application. METHODS: After obtaining Animal Research Ethics Committee approval, AO was applied in 12 piglets for 40 min. Arterial (a) and mixed venous (v) blood samples for oxygen (O2) and carbon dioxide (CO2) tension (PaO2/PvO2, PaCO2/PvCO2), O2 saturation (SaO2/SvO2), pHa, base excess (BEa), and bicarbonate (HCO3a) determination and for alveolar O2 tension (PAO2), PaO2/FiO2 and PaO2/PAO2 ratio, arterial-mixed venous O2 content (AVDO2), and O2 extraction ratio (O2ER) estimation were collected on anesthesia induction, 10, 20, 30, and 40 min during AO and 10 and 20 min after reconnection to the ventilator. Concomitant hemodynamic data were obtained. RESULTS: Besides PvO2 and PAO2, AO adversely influenced PaO2 (248-113 mmHg), PaCO2 (35-145 mmHg), PvCO2, PaO2/FiO2, and PaO2/PAO2 in a time-depended fashion, whereas SvO2, AVDO2, and O2ER were minimally affected. P(a - v)CO2 was reversed throughout AO. Acid-base status derangement, consisting of HCO3a elevation, BEa widening, and acidemia (pH 6.9) maximized 40 min after AO. During AO, heart rate, systemic and pulmonary circulation pressures, and cardiac output were progressively elevated, whereas systemic vascular resistance was reduced. All the studied parameters reverted almost to baseline within the 20-min period of ventilator reconnection. CONCLUSION: Tracheal AO for 40 min ensures acceptable blood oxygenation, promotes notable hypercapnic acidosis, and consequent transient hemodynamic alterations, which are almost completely reversible after reconnection to the ventilator.

Cerebral oxygenation impairment and S-100ß protein release during off-pump coronary artery revascularization.

OBJECTIVE: To elucidate the magnitude of global cerebral oxygenation impairment, using cerebral oxygenation indices and S-100ß protein as potential markers, during off-pump coronary artery bypass grafting (OPCAB). DESIGN: Prospective cohort study. SETTING: Tertiary cardiac center. PARTICIPANTS: Thirty-five patients undergoing OPCAB. INTERVENTIONS: Jugular bulb and arterial blood samples for cerebral oxygenation indices (arterial oxygen and carbon dioxide partial pressures, jugular bulb oxygen saturation, arterial-jugular bulb oxygen content, arterial-jugular carbon dioxide partial pressure, brain oxygen extraction ratio, and estimated respiratory quotient) and S-100ß protein determination were collected at anesthesia induction; anterior, inferior, and posterior wall anastomoses; after sternal closure; and 6 hours postoperatively. Concomitant hemodynamic data were obtained. The S-100ß determination was extended to 12 and 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Heart positioning for the target vessel exposure induced significant hemodynamic deterioration (p < 0.001). Although cerebral oxygenation indices were influenced adversely by a low-cardiac-output state mainly during vertical heart dislocation (p < 0.001), they remained within normal limits. Hemodynamic and cerebral oxygenation statuses reverted to baseline within 6 hours postoperatively. Similarly, S-100ß jugular bulb and arterial protein levels presented a gradual increase, which peaked by the end of surgery (means, 0.54 and 0.62 µg/L, respectively; p < 0.001) and then decreased by the first postoperative day. Jugular bulb-arterial S-100ß levels were maximized during posterior wall anastomosis (0.098 µg/L; p < 0.01). CONCLUSION: Although exposure of the 3 main coronary arteries during OPCAB promotes derangement of the cerebral oxygen indices and S-100ß release, this seems to be transient, remains within the near-normal range, and is reversible almost completely 6 hours postoperatively.

Correlation of central venous-arterial and mixed venous-arterial carbon dioxide tension gradient with cardiac output during neurosurgical procedures in the sitting position.

BACKGROUND AND OBJECTIVE: The study was conducted to evaluate the correlation of central venous-arterial and mixed venous-arterial pCO(2) gradient with cardiac output in patients being operated in the sitting position. METHODS: Fifty-one patients, aged 41-69 years, classified as American Society of Anesthesiologists physical status II and III, scheduled to undergo elective neurosurgical procedures in the sitting position, were enrolled in this prospective cohort study. Simultaneous blood gas samples from arterial, central venous and pulmonary artery catheters were collected at four different time points during supine and sitting position. Cardiac index (CI) determination was accomplished simultaneously, with continuous cardiac output technique. The mixed venous-arterial pCO(2) and central venous-arterial pCO(2) gradients were calculated and related to CI at the specific time points, thus a total of 204 points of comparison were obtained. RESULTS: Changing from the supine to the sitting position induced a significant deterioration of CI, right atrial pressure, mean pulmonary arterial pressure and pulmonary wedge pressure. The mean delta pCO(2) difference (bias) in the four time points ranged between -0.07 and -0.27. The upper (1.59-1.71 mmHg) and lower limits of agreement (-2.16 to -1.82 mmHg) were quite narrow, suggesting an acceptable overall agreement between the mixed and central venous pCO(2) differences. The coefficient of determination (R(2)) between the venous-arterial pCO(2) and CI for mixed and central venous circulations was 0.830 and 0.760 (P < 0.001 for both), respectively. In contrast, R(2) values between mixed and central venous oxygen saturation values and CI were 0.324 and 0.286, respectively (P < 0.001 for both), illustrating a rather weak relationship. CONCLUSION: It seems that venous-arterial pCO(2) values obtained from mixed and central venous circulations can be reliably interchanged in estimating CI in patients undergoing neurosurgical procedures in the sitting position. Thus, central venous-arterial pCO(2) gradient could serve as a useful and simple method for estimating cardiac performance, in which further invasive monitoring is not strongly indicated.

Effects of pneumoperitoneum and LPS-induced endotoxemia on cerebral perfusion pressure in pigs.

Multitrauma patients commonly develop abdominal compartment syndrome, which is defined as the end result of sustained, uncorrected, intra-abdominal hypertension. We aimed to assess the effects of increased intra-abdominal pressure (IAP) upon intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in the presence or absence of lipopolysacharide (LPS)-induced endotoxemia using an experimental porcine model of pneumoperitoneum. Experimental procedures were approved by the Animal Care Review Committee of the National Veterinary Institute. Sixteen female pigs weighing 20 to 25 kg, aged 3 to 4 months were used. The animal model of increased IAP employed in our studies was produced with intraperitoneal administration of helium at 25 mm Hg under general anesthesia. After induction of pneumoperitoneum, 16 animals were randomly divided into 2 groups of 8 pigs each. One group received LPS intravenously (endotoxin group) and the second group received saline (control group). ICP, CPP, and hemodynamic variables were continuously monitored and recorded. A significant reduction of the cardiac output and concurrent increases in systemic vascular resistance and central venous pressure were observed in both groups after induction of pneumoperitoneum. ICP increased whereas CPP decreased significantly compared with baseline values in both groups after elevation of IAP. After LPS administration (endotoxin group), the cardiac output and mean arterial pressure decreased significantly. The CPP decreased further in the endotoxin group after LPS administration, whereas ICP remained unchanged. IAP increases produce significant increases in the ICP and decreases in the CPP in this animal model. LPS-induced endotoxemia further decreased CPP.