Electrodermal Activity Monitoring During Painful Stimulation in Sedated Adult Intensive Care Unit Patients: a Pilot Study.

Introduction-Aim: Newer methods, such as infrared digital pupillometry and electrodermal activity (EDA) measurement have been suggested as good alternatives for analgesia monitoring in critically ill patients. This study analyzed EDA changes due to pain stimulus in sedated adult critical care patients Methods: Skin conductance variability, selected hemodynamic and respiratory parameters, Bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime in an adult ICU. 4h-Measurements were divided into 2 groups, based upon the sedation level of the patients: Group A - Ramsay Sedation Score 2-4 and Group B - Ramsay Sedation Score of 5-6. Selected recordings before and after pain stimulus were performed. The stimulus chosen was the pressure applied to nail bed for 10 sec, which was performed routinely during neurological examination. Patients' demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed by 2 independent observers via Critical Care Pain Observation Tool (CPOT) and Adult Non Verbal Pain Score (ANVPS) Results: In both groups the rate of EDA changes was greater than other monitoring parameters: more in Group A than in Group B. Yet, the difference between groups was not statistically significant. CONCLUSION: EDA measurements are greater to pain stimuli, than cardiovascular, respiratory or even BIS monitoring. These encouraging results suggest that, further studies are needed to better define EDA role in ICU.

Electrodermal Activity Monitoring during Endotracheal Suction in Sedated Adult Intensive Care Unit Patients.

BACKGROUND: Endotracheal suctioning of respiratory secretions is one of the most common causes of pain and discomfort in Intensive Care Unit environment. The electrical properties of the skin, also known as electrodermal activity (EDA), are considered as an indirect measure of autonomous nervous system. AIM: This study explores EDA changes during endotracheal suction in sedated adult critical care patients; and compares these changes to other monitoring parameters. MATERIALS AND METHODS: Skin conductance variability, selected hemodynamic and respiratory parameters, bispectral index (BIS) and ambient noise level, were monitored during 4 hour routine daytime intensive care nursing and treatment in an adult Intensive Care Unit. 4h-measurements were divided into 2 groups, based upon the sedation level (group A: Ramsay sedation scale 2-4 and group B: 5-6 respectively) of the patients. Selected recordings before and after endotracheal suction (stress events) were performed. Seven stress events from Group A and 17 from Group B were included for further analysis. Patients' demographics, laboratory exams and severity scores were recorded. Pain status evaluation before every event was also performed via 2 independent observers. RESULTS: In both groups the rate of EDA changes was greater than in other monitoring parameters. Yet, in group A only selected parameters were significantly changed after the start of the procedure, while in group B, every parameter showed significant change (p<0.05). Groups were similar for other co-founding factors. CONCLUSION: EDA measurements are more sensitive to stress stimuli, than cardiovascular, respiratory or even BIS monitoring. Deeper sedation seems to affect more the intensity of EDA changes during suction.

Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta-analysis.

AIMS: The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients. METHOD: A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects. RESULTS: The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%). CONCLUSIONS: The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.

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.

Comparison between the combination of gabapentin, ketamine, lornoxicam, and local ropivacaine and each of these drugs alone for pain after laparoscopic cholecystectomy: a randomized trial.

BACKGROUND: The main purpose of the study was to test whether the combination of gabapentin (600 mg 4 hours before surgery, 600 mg after 24 hours), ketamine (0.3 mg/kg before anesthesia), lornoxicam (8 mg before anesthesia and 8 mg/12 hours), and local ropivacaine (5 mL 7.5% at insertion sites) provides superior analgesia to each of these drugs alone in the first 24 hours after laparoscopic cholecystectomy. The secondary purpose was to examine whether this combination has less opioid-related side effects. METHODS: This was a 2-center randomized placebo-controlled trial. One hundred forty-eight patients, between 18 and 70 years of age, were randomly assigned to 6 groups (28 in each group) with the use of computer software: A(gabapentin/ketamine/lornoxicam/ropivacaine); B(gabapentin/placebo/placebo/placebo); C (placebo/ketamine/placebo/placebo); D (placebo/placebo/lornoxicam/placebo); E (placebo/placebo/placebo/ropivacaine); and F (placebo/placebo/placebo/placebo). Only the principal investigator was aware of patients' allocation and provided drugs and placebo in covered prefilled syringes. The primary outcome of the study was the 24-hour morphine consumption. Secondary outcomes were frequency of opioid-related side effects (nausea, vomiting, sedation, pruritus, and dysuria). RESULTS: Only groups A (6.4 mg), B (9.46 mg), and D (9.36 mg) had lower morphine consumption than control group (20.29 mg) (P < 0.001, P = 0.01, and P = 0.008, respectively). Group A was not different from B and D (P = 0.92, P = 0.93). The only difference was in episodes of nausea between groups A (n = 5) and the control group (n = 12) (P = 0.018). CONCLUSION: The combination of gabapentin, ketamine, lornoxicam, and local ropivacaine does not provide superior analgesia than gabapentin alone or lornoxicam alone after laparoscopic cholecystectomy. The combination reduces only the frequency of postoperative nausea, but larger studies are needed for safer results.

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.

Electrodermal Activity during Blood Pooling for Arterial Blood Gases Analysis in Sedated Adult Intensive Care Unit Patients.

Electrodermal activity (EDA) is considered a measure of autonomous nervous system activity. This study performed an exploratory analysis of the EDA changes during blood pooling for arterial blood gas analysis in sedated adult critical care patients and correlated the variations to other monitored parameters. EDA, along with other parameters, were monitored during 4 h routine daytime intensive care nursing and treatment in an adult ICU. 4 h measurements were divided into two groups based upon the sedation level. Selected recordings before and after blood pooling for arterial blood gases analysis (stress event) was performed. Nine stress events from Group A and 17 from Group B were included for further analysis. Patients' demographics, laboratory exams, and severity scores were recorded. For both sedation levels, EDA changes are much greater than any other monitoring parameters used. The changes are noticed in both measurement (15 s and 60 s), even though in the 60 s measurement only selected EDA parameters are significantly changed after the start of the procedure. EDA measurements are more sensitive to a given stress event than cardiovascular or respiratory parameters. However, the present results could only be considered as a pilot study. More studies are needed in order to identify the real stress-load and clinical significance of such stimuli, which are considered otherwise painless in those patients.

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.

Postoperative analgesia after low-frequency electroacupuncture as adjunctive treatment in inguinal hernia surgery with abdominal wall mesh reconstruction.

OBJECTIVE: To determine whether an electroacupuncture (EA) technique that was developed for a surgical population under general anaesthesia reduces pain after mesh inguinal hernia open repair. METHODS: A total of 54 patients with right or left inguinal hernia were randomised to group I (preoperative, intraoperative, postoperative EA), group II (preoperative, postoperative EA), or a sham control group (group III; preoperative and postoperative placement of needles, but without skin penetration). The Visual Analogue Scale (VAS) (primary outcome) and the State-Trait Anxiety Spielberger Inventory were evaluated preoperatively and at 30 min, 90 min, 10 h and 24 h after surgery. Pain threshold and tolerance were evaluated using an algometer at these same time points and preoperatively before and after EA. Levels of the stress hormones cortisol, corticotrophin and prolactin were determined at 30 min, 90 min and 10 h after surgery and preoperatively before and after EA. RESULTS: The results showed significant differences between the true EA and control groups. The true EA groups (I and II) showed statistically significantly greater improvements in the primary (VAS pain, p<0.05) and secondary outcome measures (Anxiety scale; algometer measurements, p<0.05 and stress hormones, p<0.01) compared to the control group. There were no statistically significant differences between groups I and II. CONCLUSIONS: Electroacupuncture reduces postoperative pain after mesh inguinal hernia repair and decreases stress hormone levels and anxiety during the postoperative period. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT01722253.