The safety and efficacy of spinal anesthesia for surgery in infants: the Vermont Infant Spinal Registry

Studies with modest numbers of patients have suggested that spinal anesthesia in infants is associated with a very infrequent incidence of complications, such as hypoxemia, bradycardia, and postoperative apnea. Although spinal anesthesia would seem to be a logical alternative to general anesthesia for many surgical procedures, it remains an underutilized technique. Since 1978, clinical data concerning all infants undergoing spinal anesthesia at the University of Vermont have been prospectively recorded. In all, 1554 patients have been studied. Anesthesia was performed by anesthesia trainees and attending anesthesiologists. The success rate for LP was 97.4%. An adequate level of spinal anesthesia was achieved in 95.4% of cases. The average time required to induce spinal anesthesia was 10 min. Oxygen hemoglobin desaturation to <90% was observed in 10 patients. Bradycardia (heart rate <100 bpm) occurred in 24 patients (1.6%). This study confirms the infrequent incidence of complications associated with spinal anesthesia in infants. Spinal anesthesia can be performed safely, efficiently, and with the expectation of a high degree of success. Spinal anesthesia should be strongly considered as an alternative to general anesthesia for lower abdominal and lower extremity surgery in infants.     

Portomesenteric Venous Thrombectomy Using Inari Triever Aspiration Catheter (FlowTriever)

CardioVascular and Interventional Radiology -     

A double-blind, placebo-controlled, efficacy, safety, and pharmacokinetic study of INN 00835, a novel antidepressant peptide, in the treatment of major depression

BACKGROUND: INN 00835 is a synthetic pentapeptide with a potential for rapid onset of action as an antidepressant. Its efficacy was investigated in a pilot study in patients diagnosed with major depression. METHODS: Fifty two patients received either active drug - INN 00835 (26 patients) - or placebo (26 patients), subcutaneously at 0.2 mg/kg for 5 consecutive days. The patients were evaluated for an additional 4 weeks after treatment. Efficacy was evaluated by the following psychiatric rating scales: HAMD, MADRS, CSRS, CGI, and VAS. The effect of treatment was also evaluated by using a biochemical marker: changes in blood platelet serotonin (5HT) uptake rates in drug-treated patients compared to those in the placebo group. Plasma concentrations of INN 00835 were measured by LC/MS. RESULTS: Statistical analysis indicated a strong pharmacodynamic correlation between plasma drug concentrations at 1 h after dosing and the reduction in the severity of depression as measured by the psychiatric rating scales. A minimum effective plasma concentration (MEC) of INN 00835 was 5 ng/ml. Statistically significant differences in response to treatment (P<0.05) were found between patients with plasma concentrations above MEC and those in the placebo group, as well as between subjects with plasma concentrations above and below the MEC. The peak effect was observed after the 5-day treatment and the response to treatment persisted during the 4-week follow-up period. The change of 5HT uptake rates after treatment was significantly larger in the drug-treated group than in the placebo group. Limitations: This was a pilot study conducted in a relatively small population (52 patients) and the limited number of blood sampling times did not allow a comprehensive pharmacokinetic analysis. There was a relatively large placebo response. The results have to be confirmed in future, large scale studies. CONCLUSIONS: INN 00835 appears to be a promising drug for the treatment of major depression.     

Clinical effectiveness of nemifitide,a novel pentapeptide antidepressant,in depressed outpatients: comparison of follow-up re-treatment with initial treatment

Data from two Phase 2 clinical studies with nemifitide, a novel pentapeptide antidepressant, were evaluated. The initial double-blind, placebo-controlled study was performed on outpatients with DSM-IV criteria for major depressive disorder. An open-label extension study enrolled subjects either completing or having been discontinued due to lack of efficacy during the follow-up period of the initial study. In the extension study, both the investigator and the subjects were blinded to the previous treatment in the initial study. No clinically significant side-effects were observed in either study. Twenty-seven subjects have been entered and evaluated in the extension study. Eighteen of these 27 subjects (66.7%) responded to re-treatment in the extension study. Mean duration of effect between re-treatments was 3.3 months. The results of the extension study support investigating a range of doses of nemifitide from 18 to 72 mg/d in future clinical trials. Further studies are planned to determine the most effective nemifitide clinical treatment regimen.     

Combined spinal and epidural anaesthesia for major abdominal surgery in infants

Purpose

Subarachnoid anaesthesia is becoming increasingly popular in neonates and infants. However, single dose spinal anaesthesia is of limited value for major abdominal surgery in infants due to its short duration of action and inability to provide analgesia in the post operative period. A new technique of combined spinal and epidural anaesthesia for major abdominal surgery in the infant is described.

Methods

Data were gathered prospectivety from 19 infants presenting for upper and lower abdominal surgery. Anaesthesia was induced with a subarachnoid injection of tetracaine. After the subarachnoid block was established, an epidural catheter was placed for further intraoperative and postoperative management. Data collected included age and weight of the patients, type and duration of the surgical procedure. Doses of local anaesthetics as well as the need for intraoperative and postoperative supplements were recorded. An illustrative case report is provided.

Results

Infants studied represented a wide range of weights (1520–7840 g). Spinal anaesthesia was successful in all 19 patients. A variety of extensive surgical procedures including small bowel resections and various genitounnary procedures were successfully performed. In 17 patients a functioning epidural catheter was in place postoperatively. In these patients effective analgesia was maintained with dilute solutions of epidural bupivacaine. Only three doses of narcotic were required for pain control. No patient required postoperative mechanical ventilation or tracheal intubation.

Conclusion

Combined spinal and epidural anaesthesia is a potential option to general anaesthesia for major abdominal surgery in infants.     

Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo electron paramagnetic resonance study

Exposure to high altitude or hypobaric hypoxia results in a series of metabolic, physiologic, and genetic changes that serve to acclimate the brain to hypoxia. Tissue Po(2) (Pto(2)) is a sensitive index of the balance between oxygen delivery and utilization and can be considered to represent the summation of such factors as cerebral blood flow, capillary density, hematocrit, arterial Po(2), and metabolic rate. As such, it can be used as a marker of the extent of acclimation. We developed a method using electron paramagnetic resonance (EPR) to measure Pto(2) in unanesthetized subjects with a chronically implanted sensor. EPR was used to measure rat cortical tissue Pto(2) in awake rats during acute hypoxia and over a time course of acclimation and deacclimation to hypobaric hypoxia. This was done to simulate the effects on brain Pto(2) of traveling to altitude for a limited period. Acute reduction of inspired O(2) to 10% caused a decline from 26.7?±?2.2 to 13.0?±?1.5?mmHg (mean?±?SD). Addition of 10% CO(2) to animals breathing 10% O(2) returned Pto(2) to values measured while breathing 21% O(2,) indicating that hypercapnia can reverse the effects of acute hypoxia. Pto(2) in animals acclimated to 10% O(2) was similar to that measured preacclimation when breathing 21% O(2). Using a novel, individualized statistical model, it was shown that the T(1/2) of the Pto(2) response during exposure to chronic hypoxia was approximately 2 days. This indicates a capacity for rapid adaptation to hypoxia. When subjects were returned to normoxia, there was a transient hyperoxygenation, followed by a return to lower values with a T(1/2) of deacclimation of 1.5 to 3 days. These data indicate that exposure to hypoxia results in significant improvements in steady-state oxygenation for a given inspired O(2) and that both acclimation and deacclimation can occur within days.     

Measurement of the oxidation state of mitochondrial cytochrome c from the neocortex of the mammalian brain

Diffuse optical remission spectra from the mammalian neocortex at visible wavelengths contain spectral features originating from the mitochondria. A new algorithm is presented, based on analytically relating the first differential of the attenuation spectrum to the first differential of the chromophore spectra, that can separate and calculate the oxidation state of cytochrome c as well as the absolute concentration and saturation of hemoglobin. The algorithm is validated in phantoms and then tested on the neocortex of the rat during an anoxic challenge. Implementation of the algorithm will provide detailed information of mitochondrial oxygenation and mitochondrial function in physiological studies of the mammalian brain.