Arterial pressure control with isoflurane using fuzzy logic

Arterial pressure is still one of the most important measures in estimating the required dose of inhaled anaesthetics. It is measured easily and reacts rapidly which makes it suitable as a variable for feedback control of depth of anaesthesia. Fuzzy logic, a novel approach to feedback control, was used to control arterial pressure in 10 patients during intra-abdominal surgery by automatic adjustment of the concentration of isoflurane in fresh gas. During anaesthesia, fuzzy control periods of 45-min duration were alternated randomly with human control periods of equal duration. During the skin incision period (−3 to +12min) 48.2% of all fuzzy control pressure values were within ±10% of the desired mean arterial pressure compared with 40.4% of the human control values (P < 0.05). The corresponding values for the remainder of the operation were 78.3% and 83.2%, respectively. Thus fuzzy outperformed human control at skin incision, but was slightly inferior during the rest of the operation. We conclude that fuzzy logic is a promising new technique for control of isoflurane delivery during routine anaesthesi

Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation

Background. Hypnotic depth but not haemodynamic response to painful stimulation can be measured with various EEG-based anaesthesia monitors. We evaluated the variation of pulse plethysmography amplitude induced by an electrical tetanic stimulus (PPG variation) as a potential measure for analgesia and predictor of haemodynamic responsiveness during general anaesthesia. Methods. Ninety-five patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml−1;Group 2: BIS 40-50, remifentanil 2 ng ml−1; Group 3: BIS 40-50, remifentanil 4 ng ml−1; Group 4: BIS 25-35, remifentanil 2 ng ml−1; Group 5: BIS 55-65, remifentanil 2 ng ml−1]. A 60 mA tetanic stimulus was applied for 5 s on the ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop computer, linear and non-linear parameters of PPG variation during the 60 s period after stimulation were computed. The haemodynamic response to subsequent orotracheal intubation was recorded. The PPG variation was compared between groups and between responders and non-responders to intubation (anova). Variables independently predicting the response were determined by logistic regression. Results. The probability of a response to tracheal intubation was 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was significantly higher in responders than in non-responders but it did not improve the prediction of the response to tracheal intubation based on BIS level and effect site remifentanil concentration. Conclusion. Tetanic stimulation induced PPG variation does not reflect the analgesic state in a wide clinical range of surgical anaesthesi

Heart rate variability does not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia†

Background Hypnotic depth but not haemodynamic responsiveness is measured with EEG-based monitors. In this study we compared heart rate variability (HRV) in unstimulated patients and stimulation-induced HRV at different levels of anaesthesia. Methods A total of 95 ASA I or II patients were randomly assigned to five groups (Group 1: BIS 45(5), remifentanil 1 ng ml−1; Group 2: BIS 45(5), remifentanil 2 ng ml−1; Group 3: BIS 45(5), remifentanil 4 ng ml−1; Group 4: BIS 30(5), remifentanil 2 ng ml−1; Group 5: BIS 60(5), remifentanil 2 ng ml−1). A time- and frequency-domain analysis of the RR interval (RRI) from the electrocardiogram was performed. HRV before induction, before and after a 5 s tetanic stimulus of the ulnar nerve, and before and after tracheal intubation was compared between groups, between stimuli, and between responders to intubation [systolic arterial pressure (SAP) increase >20 mm Hg, a maximal heart rate (HR) after intubation >90 min−1 or both] and non-responders (anova). Results Induction of anaesthesia significantly lowered HR and HRV. Mean RRI before stimulation was higher in G3 than in G1, G2, and G4 (P < 0.001), whereas the other HRV parameters were similar. Intubation induced a greater HRV response than tetanic stimulation. The mean RRI after intubation was lower in G3 compared with the other groups and the sd of the RRI after tetanic stimulation was lower in G3 compared with G5. Otherwise, unstimulated HRV and stimulation-induced HRV were similar in responders and non-responders. Conclusion HRV parameters discriminate between awake and general anaesthesia, are different after tracheal intubation and a 5 s ulnar nerve stimulation, but do not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesi

A Meta-Analysis of Clinical Advancement in Sanfilippo Syndrome Type A

Sanfilippo syndrome (also known as MPS III) type A is caused by the mutation of gene SGSH on chromosome 17, region 17q25.3. Sanfilippo syndrome is a recessive gene affecting 1 in 70,000 babies each year. This mutation affects the mucopolysaccharides and causes the patient to lose an enzyme that is crucial to breaking down the mucopolysaccharide heparan sulfate. Heparan sulfate is stored in the cells instead of being broken down, causing progressive damage. Symptoms become apparent after the age of 1-year-old and learning abilities decline between the ages of 2 and 6. The symptoms and progression rate are different in each patient. Eventually, physical growth slows, resulting in small stature. Some other common symptoms include behavioral problems, coarse facial features, full lips, heavy eyebrows, sleep difficulties, stiff joints, and difficulty walking. There is no known cure and no approved treatment for MPS III. Bone marrow transplants and enzyme replacement therapy have not been effective in treating MPS III. Currently, gene therapy, chaperone therapy, and intrathecal enzyme therapy are being explored as treatments for Sanfilippo syndrome

Lumbar epidural fentanyl: segmental spread and effect on temporal summation and muscle pain

Background. Despite extensive use, different aspects of the pharmacological action of epidural fentanyl have not been clarified. We applied a multi‐modal sensory test procedure to investigate the effect of epidural fentanyl on segmental spread, temporal summation (as a measure for short‐lasting central hyperexcitability) and muscle pain. Methods. Thirty patients received either placebo, 50 or 100 µg single dose of fentanyl epidurally (L2-3), in a randomized, double‐blind fashion. Heat pain tolerance thresholds at eight dermatomes from S1 to fifth cranial nerve (assessment of segmental spread), pain threshold to transcutaneous repeated electrical stimulation of the sural nerve (assessment of temporal summation) and pain intensity after injection of hypertonic saline into the tibialis anterior muscle (assessment of muscle pain) were recorded. Results. Fentanyl 100 µg, but not 50 µg, produced analgesia to heat stimulation only at L2. Surprisingly, no effect at S1 was detected. Both fentanyl doses significantly increased temporal summation threshold and decreased muscle pain intensity. Conclusions. The findings suggest that a single lumbar epidural dose of fentanyl should be injected at the spinal interspace corresponding to the dermatomal site of pain. Increased effect on L2 compared with S1 suggests that drug effect on spinal nerve roots and binding to opioid receptors on the dorsal root ganglia may be more important than traditionally believed for the segmental effect of epidurally injected fentanyl. Epidural fentanyl increases temporal summation threshold and could therefore contribute to prevention and treatment of central hypersensitivity states. I.M. injection of hypertonic saline is a sensitive technique for detecting the analgesic action of epidural opioids. Br J Anaesth 2003; 90: 467-7

Ondansetron does not inhibit the analgesic effect of alfentanil

5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, doubleblind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron- alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentani

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties