Computations Reveal That Electron-Withdrawing Leaving Groups Facilitate Intramolecular Conjugate Displacement Reactions by Negative Hyperconjugation.

Intramolecular conjugate displacement (ICD) reactions, developed by the Clive group, form carbocycles and polycyclic amines by intramolecular nucleophilic attack on a Michael acceptor with an allylic leaving group. Quantum mechanical investigations with density functional theory show that ICDs involve a stepwise addition, forming an intermediate stabilized carbanion, followed by elimination. The electron-withdrawing nature of the allylic leaving group facilitates the addition by negative hyperconjugation; the twist-boat conformation of the addition and intermediate is stabilized by this interaction. In the absence of an activating electron-withdrawing group as part of the Michael acceptor, a high energy concerted SN2' reaction occurs. The reactions of carbon nucleophiles have lower activation energies than those of amines.

Superior mesenteric artery syndrome following surgery for adolescent idiopathic scoliosis: a case series, review of the literature, and an algorithm for management.

Superior mesenteric artery (SMA) syndrome is a rare but potentially fatal complication following spinal fusion for scoliosis. The aims of our study were to identify clinical features and evaluate their importance in SMA syndrome following posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS) patients and to recommend a simple approach for the recognition and management of SMA syndrome. This is an IRB-approved study. Three patients in our series and 11 patients from other published case reports who underwent PSF for adolescent idiopathic scoliosis were included in our study. Patient demographics, clinical presentation, investigations, and management were recorded and analyzed. In this combined series of 14 patients (mean age 14.8 years), the main presenting clinical features included vomiting of any kind (92.9%), abdominal pain/tenderness (57.1%), abdominal distension (42.9%), bilious vomiting (35.7%), and hypoactive bowel sounds (28.6%). Most patients presented within 2 weeks of surgery (71.4%). In total, 50% of patients presented with both vomiting (of any kind) and abdominal tenderness. The number of presenting symptoms appeared to be directly related to the severity of SMA syndrome. Our second patient had intermittent vomiting on postoperative day (POD) 3, which was initially considered as insignificant; she was discharged on POD 9 and readmitted for recurrent vomiting, during which SMA syndrome was diagnosed. Our first patient presented in the classical manner. Our third patient had bilious vomiting after discharge that started on POD 13 and increased in frequency until readmission on POD 27. Vomiting and abdominal pain are nonspecific symptoms following PSF; differentiating between SMA syndrome and postoperative ileus can be challenging. The highest index of suspicion applies to patients who present within the first week with symptoms of vomiting and abdominal pain. We propose an algorithm for the management of SMA syndrome, which includes a focused clinical assessment to evaluate for intestinal obstruction, followed by an abdominal radiography and barium contrast study if clinical assessment is positive. An early referral to general surgery should be considered especially for high-risk patients (BMI<5% percentile, sagittal kyphosis). Early diagnosis of SMA syndrome allows for early intervention, reducing the likelihood of future complications and need for surgery.

Protecting staff against airborne viral particles: in vivo efficiency of laser masks.

Laser masks are used to prevent inhalation of viral particles during laser surgery. A crossover trial was performed in eight volunteers to compare the ability of a surgical mask and a laser mask with that of an FFP2 respirator to filter airborne dust particles. The surgical and laser masks were tested when worn normally and when they were taped to the face. The mean reductions in particle counts were 3.0 fold [95% confidence interval (95% CI) 1.8-4.2] for the untaped surgical mask, 3.8 fold (95% CI 2.9-4.6) for the untaped laser mask, 7.5 fold (95% CI 6.5-8.5) for the taped surgical mask, 15.6 fold (95% CI 13.5-17.8) for the taped laser mask, and 102.6 fold (95% CI 41.2-164.1) for the FFP2 half-face respirator. The laser mask provided significantly less protection than the FFP2 respirator (P=0.02), and only marginally more protection than the surgical mask. The continued use of laser masks for respiratory protection is questionable. Taping masks to the face only provided a small improvement in protection.

Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks.

Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organisation state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected severe acute respiratory syndrome (SARS). In areas where N95 masks are not available, multiple layers of surgical masks have been tried to prevent transmission of SARS. The in vivo filtration capacity of a single surgical mask is known to be poor. However, the filtration capacity of a combination of masks is unknown. This was a crossover trial of one, two, three and five surgical masks in six volunteers to determine the in vivo filtration efficiency of wearing more than one surgical mask. We used a Portacount to measure the difference in ambient particle counts inside and outside the masks. The best combination of five surgical masks scored a fit factor of 13.7, which is well below the minimum level of 100 required for a half face respirator. Multiple surgical masks filter ambient particles poorly. They should not be used as a substitute for N95 masks unless there is no alternative.

Predictive value of the user seal check in determining half-face respirator fit.

Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organization state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected cases of severe acute respiratory syndrome. Before use, the manufacturer recommends performing a user seal check to ensure that the mask is fitted correctly. This study aimed to test the ability of the user seal check to detect poorly fitting masks. This study is a retrospective review of a mask-fitting programme carried out in the intensive care unit of the Prince of Wales Hospital in Hong Kong. In this programme, all staff were tested with two types of N95 mask and one type of N100 mask. The results of the documented user seal check were then compared with the formal fit-test results from a PortaCount. Using a PortaCount reading of 100 as the criterion for a correctly fitted mask, the user seal check wrongly indicated that the mask fitted on 18-31% of occasions, and wrongly indicated that it did not fit on 21-40% of occasions. These data indicate that the user seal check should not be used as a surrogate fit test. Its usefulness as a pre-use test must also be questioned.

Consequences of syringe size sensor malfunction in a modern infusion pump.

Prompted by an actual case of potentially life-threatening infusion pump malfunction, we investigated the effects of wire breakage(s) within the syringe size sensor circuit in a Graseby 3400 infusion pump. The circuit wires within the sensor were systematically broken. The syringe sizes recognised by the sabotaged circuit and the actual sizes of syringes inserted into the pump were compared. Thirty-eight per cent of the possible wire breakages resulted in a smaller syringe size being recognized, causing the infusion rate to be too fast, and 38% of the possiblewire breakage resulted in a larger syringe size being recognized, causing the infusion rate to be too slow. The volume delivered for each different size of Terumo syringe as a function of distance travelled by the plunger was measured. The errors ranged from 0.4 to 2.6 times that of the expected rate. Only 1.3% of the possible wire breakage(s) were recognised as errors by the pump. The infusion rates were not affected in 22.5% of the cases. Wire breakage within the syringe size sensor in infusion pumps is yet another potential source of infusion error, with important safety implications.

A pharmacokinetic model for factor VIII dosing during active haemorrhage in patients with haemophilia A.

A theoretical one-compartment pharmacokinetic model is described, the aim of which is to guide factor VIII replacement therapy in patients with haemophilia A suffering from significant and ongoing haemorrhage. Based on our calculations, plasma factor VIII concentrations can decrease at a rapid rate even with non-severe blood loss.

A comparison of three fluid-vasopressor regimens used to prevent hypotension during subarachnoid anaesthesia in the elderly.

We aimed to compare the efficacy of fluid preloading with two recently recommended fluid-vasopressor regimens for maintaining blood pressure during subarachnoid anaesthesia in the elderly. Sixty elderly patients requiring surgery for traumatic hip fractures received subarachnoid anaesthesia using 0.05 ml/kg of 0.5% heavy bupivacaine. Hypotension, i.e. systolic arterial pressure < 75% of baseline, was prevented or treated by: A--normal saline 16 ml/kg plus intravenous ephedrine boluses (0.1 mg/kg); B--normal saline 8 ml/kg plus intramuscular depot ephedrine (0.5 mg/kg); or C--Haemaccel 8 ml/kg plus metaraminol infusion. Systolic arterial pressure and heart rate were recorded using custom-written computer software (Monitor, version 1.0). Systolic arterial pressure decreased in all groups after five minutes (P < 0.001). Decreases were greatest in group A (P < 0.05). Heart rate increased by 7% group A and decreased by 9% in group C (P < 0.05). During the first hour, hypotension was present for 47%, 25% and 20% of the time in groups A, B and C respectively and overcorrection of systolic arterial pressure occurred in 19% of the time in group C. We conclude that treatment A was inadequate in preventing hypotension. Treatments B and C were more effective but were associated with an increased heart rate and overcorrection of systolic arterial pressure respectively.

The application of a modified proportional-derivative control algorithm to arterial pressure alarms in anesthesiology.

OBJECTIVE: We have developed an arterial pressure alarm system based on a modified proportional-derivative (PD) controller algorithm, and prospectively tested its ability to predict significant hypotensive episodes, defined as systolic arterial pressure < 80 mmHg, in comparison to conventional limit alarms. METHODS: The alarm algorithm was tuned to detect hypotension using selected invasive arterial pressure traces taken from ten patients who had large intra-operative arterial pressure changes. The algorithm's performance was then tested prospectively in comparison to conventional limit alarms and median filtered limit alarms, set at 85 mmHg and 90 mmHg, for its ability to predict hypotensive episodes in a further 100 patients who required invasive arterial pressure monitoring. RESULTS: For the PD alarm algorithm, onset times for significant hypotensive episodes were between those of limit alarms set at 85 mmHg and 90 mmHg. Offset times were similar to the 85 mmHg limit alarms. The false positive rate was 34% compared with 45-64% for the other alarms (p < 0.01). Using our definitions, there was one false negative in the PD group, being a 15 second drop in observed arterial pressure, when a non invasive blood pressure cuff was inflated above the arterial line. CONCLUSIONS: An arterial pressure alarm system design based on a closed loop control algorithm offered improved perform ance over conventional limit alarms and in addition provided a graded output of severity of the hypotension.

Postpartum patients have slightly prolonged neuromuscular block after mivacurium.

UNLABELLED: Postpartum patients have decreased plasma cholinesterase activity, which may slow the metabolism of mivacurium. We compared the duration of a mivacurium neuromuscular block in 11 women undergoing postpartum tubal ligation 36-99 h after delivery with that in 11 control women undergoing gynecological surgery. Anesthesia was induced with propofol and fentanyl and maintained with propofol and nitrous oxide. Neuromuscular block was monitored by electromyography, and the ulnar nerve was stimulated transcutaneously using a train-of-four pattern. Patients received a bolus dose of mivacurium 0.15 mg/kg. The median (range) duration of neuromuscular block until 25% recovery of the first twitch response was longer in the postpartum group, 19.4 (15.6-25.2) min, compared with the control group, 16.3 (11.0-23.4) min (P = 0.04). The median (range) plasma cholinesterase activity was decreased in the postpartum group, 4.0 (0.1-5.5) kU/L, compared with the control group, 7.1 (6.2-10.0) kU/L (P < 0.001). The duration of neuromuscular block was inversely correlated with cholinesterase activity (Kendall rank correlation tau = -0.43, P = 0.005). The slight prolongation of neuromuscular block should not be significant clinically. IMPLICATIONS: Postpartum patients have decreased amounts of the plasma cholinesterase enzyme. This would slow the metabolism of the muscle relaxant mivacurium. However, the duration of muscle paralysis is only prolonged by approximately 3 min, which would not normally cause any significant problems.

Sampling intervals to record severe hypotensive and hypoxic episodes in anesthetised patients.

OBJECTIVE: To define the longest sampling interval which will faithfully record the time course of episodes of severe hypotension and hypoxia in anesthetised patients. METHODS: Electronic anesthetic records of 1501 patients were analyzed retrospectively for hypotension where measured systolic blood pressure fell to 60 mmHg or less, and for hypoxia where SpO2 fell to 80% or less. The onset and offset times, maximum rate of change and spectral content were calculated for each episode. RESULTS: These episodes commonly were rapid in onset and offset. The longest sampling interval to accurately represent these data was calculated to be 36 s for invasive blood pressure and 13 s for pulse oximetry. CONCLUSIONS: Our current anesthetic record is inadequate to record many of the severe changes that we observed. One minute recording intervals, such as used in many electronic record keeping systems, are too slow to capture the rapid rates of change seen, and may lead to the assumption that an episode was not recognized promptly or that treatment was not administered in a timely manner.