Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.

During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 microns), a GABAA receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABAA receptor blockers bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 microns). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABAA autoreceptor activation.

A Randomized Trial for the Treatment of Refractory Status Epilepticus.

BACKGROUND: Refractory status epilepticus (RSE) has a mortality of 16-39%; coma induction is advocated for its management, but no comparative study has been performed. We aimed to assess the effectiveness (RSE control, adverse events) of the first course of propofol versus barbiturates in the treatment of RSE. METHODS: In this randomized, single blind, multi-center trial studying adults with RSE not due to cerebral anoxia, medications were titrated toward EEG burst-suppression for 36-48 h and then progressively weaned. The primary endpoint was the proportion of patients with RSE controlled after a first course of study medication; secondary endpoints included tolerability measures. RESULTS: The trial was terminated after 3 years, with only 24 patients recruited of the 150 needed; 14 subjects received propofol, 9 barbiturates. The primary endpoint was reached in 43% in the propofol versus 22% in the barbiturates arm (P = 0.40). Mortality (43 vs. 34%; P = 1.00) and return to baseline clinical conditions at 3 months (36 vs. 44%; P = 1.00) were similar. While infections and arterial hypotension did not differ between groups, barbiturate use was associated with a significantly longer mechanical ventilation (P = 0.03). A non-fatal propofol infusion syndrome was detected in one patient, while one subject died of bowel ischemia after barbiturates. DISCUSSION: Although undersampled, this trial shows significantly longer mechanical ventilation with barbiturates and the occurrence of severe treatment-related complications in both arms. We describe practical issues necessary for the success of future studies needed to improve the current unsatisfactory state of evidence.

Hypertension and intra-operative incidents: a multicentre study of 125,000 surgical procedures in Swiss hospitals.

It is debated whether chronic hypertension increases the risk of cardiovascular incidents during anaesthesia. We studied all elective surgical operations performed in adults under general or regional anaesthesia between 2000 and 2004, in 24 hospitals collecting computerised clinical data on all anaesthetics since 1996. The focus was on cardiovascular incidents, though other anaesthesia-related incidents were also evaluated. Among 124,939 interventions, 27,881 (22%) were performed in hypertensive patients. At least one cardiovascular incident occurred in 7549 interventions (6% (95% CI 5.9-6.2%)). The average adjusted odds ratio of cardiovascular risk for chronic hypertension was 1.38 (95% CI 1.27-1.49). However, across hospitals, adjusted odd ratios varied from 0.41 up to 2.25. Hypertension did not increase the risk of other incidents. Hypertensive patients are still at risk of intra-operative cardiovascular incidents, while risk heterogeneity across hospitals, despite taking account of casemix and hospital characteristics, suggests variations in anaesthetic practices.

Evaluación de un nuevo método de sutura para la cirugía endoscopica transluminal a través de orificios naturales en un modelo animal

Natural Orifice Transluminal Endoscopic Surgery (NOTES) is a novel, potentially less invasive alternative to laparoscopic surgery. However, the problems of transluminal access and closure represent significant obstacles to its successful introduction in humans. Objective: to evaluate the feasibility and safety of a novel device designed for transluminal access and closure in a survival porcine model. Subjects: Four adult female Yorkshire pigs were used in the study. Interventions: While under general anesthesia, the animals were prepared with multiple tap water enemas followed by instillation of an antibiotic suspension and povidone-iodine lavage. At a distance of 15 to 20 cm from the anus, the prototype device (LSI Solutions, Victor, NY, USA) deployed a circumscribing purse-string suture around the planned incision site and subsequently used a blade mechanism to create a 2.5-cm linear incision. The transcolonic incision was then closed by cinching and securing the purse-string suture with a titanium knot by use of a separate hand-activated suture-locking device. Main Outcome Measurements: The animals were monitored daily for signs of peritonitis and sepsis and were survived for 14 days. The peritoneal cavity was examined for peritonitis, and the colonic incision site was examined for wound dehiscence, pericolic abscess formation, and gross adhesions. Tissue samples from both incisional and random peritoneal sites were obtained for histologic examination. Results: Transcolonic incision and closure were successful in all 4 animals. The device performed in a rapid and reproducible fashion. All animals recovered without septic complications. At necropsy, there was no evidence of peritonitis, abscesses, or wound dehiscence. Salpingocolonic and colovesicular adhesions were noted in 3 of 4 animals. Histologic examination revealed microabscesses at the incision site in all animals. Conclusions: The prototype incision and closure device represents a promising solution to the problems of transluminal access for NOTES. The presence of incision-related adhesions and microabscesses signal the need for further refinement in aseptic technique. 

Sedació intravenosa per procediments endoscòpics digestius: satisfacció dels pacients i perfil de seguretat.

o INTRODUCCIÓN: Las exploraciones endoscópicas digestivas son molestas para el paciente. El objetivo principal del trabajo es evaluar la satisfacción de los pacientes después de la sedación por un anestesiólogo. MATERIAL Y MÉTODO: se seleccionaron 50 pacientes. Se administró una pauta de sedoanalgesia con midazolam, fentanilo y propofol. RESULTADOS: Ningún paciente precisó ventilación manual. La complicación más frecuente al alta fue dolor abdominal. Todos los pacientes valoraron la experiencia como buena o muy buena. CONCLUSIONES: La sedación intravenosa para endoscopias digestivas aumenta la satisfacción de los pacientes, manteniendo un perfil de seguridad adecuado.

Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients.

BACKGROUND: Cerebral cholinergic transmission plays a key role in cognitive function, and anticholinergic drugs administered during the perioperative phase are a hypothetical cause of postoperative cognitive dysfunction (POCD). We hypothesized that a perioperative increase in serum anticholinergic activity (SAA) is associated with POCD in elderly patients. METHODS: Seventy-nine patients aged >65 years undergoing elective major surgery under standardized general anesthesia (thiopental, sevoflurane, fentanyl, and atracurium) were investigated. Cognitive functions were assessed preoperatively and 7 days postoperatively using the extended version of the CERAD-Neuropsychological Assessment Battery. POCD was defined as a postoperative decline >1 z-score in at least 2 test variables. SAA was measured preoperatively and 7 days postoperatively at the time of cognitive testing. Hodges-Lehmann median differences and their 95% confidence intervals were calculated for between-group comparisons. RESULTS: Of the patients who completed the study, 46% developed POCD. Patients with POCD were slightly older and less educated than patients without POCD. There were no relevant differences between patients with and without POCD regarding gender, demographically corrected baseline cognitive functions, and duration of anesthesia. There were no large differences between patients with and without POCD regarding SAA preoperatively (pmol/mL, median [interquartile range]/median difference [95% CI], P; 1.14 [0.72, 2.37] vs 1.13 [0.68, 1.68]/0.12 [-0.31, 0.57], P = 0.56), SAA 7 days postoperatively (1.32 [0.68, 2.59] vs 0.97 [0.65, 1.83]/0.25 [-0.26, 0.81], P = 0.37), or changes in SAA (0.08 [-0.50, 0.70] vs -0.02 [-0.53, 0.41]/0.1 [-0.31, 0.52], P = 0.62). There was no significant relationship between changes in SAA and changes in cognitive function (Spearman rank correlation coefficient preoperatively of 0.03 [95% CI, -0.21, 0.26] and postoperatively of -0.002 [95% CI, -0.24, 0.23]). CONCLUSIONS: In this panel of patients with low baseline SAA and clinically insignificant perioperative anticholinergic burden, although a relationship cannot be excluded in some patients, our analysis suggests that POCD is probably not a substantial consequence of anticholinergic medications administered perioperatively but rather due to other mechanisms.

Fonction surrénalienne après bolus d'étomidate en chirurgie cardiaque: une étude rétrospective [Adrenal function after induction of cardiac surgery patients with etomidate: a retrospective study]

OBJECTIVE: A single bolus dose of etomidate decreases cortisol synthesis by inhibiting the 11-beta hydroxylase, a mitochondrial enzyme in the final step of cortisol synthesis. In our institution, all the patients undergoing cardiac surgery receive etomidate at anesthesia induction. The purpose of this study was to assess the incidence of adrenocortical dysfunction after a single dose of etomidate in selected patients undergoing major cardiac surgery and requiring high-dose norepinephrine postoperatively. STUDY DESIGN: Retrospective descriptive study in the surgical ICU of a university hospital. PATIENTS AND METHODS: Sixty-three patients presented acute circulatory failure requiring norepinephrine (>0,2 microg/kg/min) during the 48 hours following cardiac surgery. Absolute adrenal insufficiency was defined as a basal cortisol below 414 nmo/l (15 microg/dl) and relative adrenal insufficiency as a basal plasma cortisol between 414 nmo/l (15 microg/dl) and 938 nmo/l (34 microg/dl) with an incremental response after 250 microg of synthetic corticotropin (measured at 60 minutes) below 250 nmol/l (9 microg/dl). RESULTS: Fourteen patients (22%) had normal corticotropin test results, 10 (16%) had absolute and 39 (62%) relative adrenal insufficiency. All patients received a low-dose steroid substitution after the corticotropin test. Substituted patients had similar clinical outcomes compared to patients with normal adrenal function. CONCLUSION: A high incidence of relative adrenal failure was observed in selected cardiac surgery patients with acute postoperative circulatory failure.

Vom Finanz- zum Wissenschaftsbetrug : Methode, den Irrungen in der medizinischen Literatur beizukommen [From financial to scientific fraud : Methods to detect discrepancies in the medical literature].

Fraud is as old as Mankind. There are an enormous number of historical documents which show the interaction between truth and untruth; therefore it is not really surprising that the prevalence of publication discrepancies is increasing. More surprising is that new cases especially in the medical field generate such a huge astonishment. In financial mathematics a statistical tool for detection of fraud is known which uses the knowledge of Newcomb and Benford regarding the distribution of natural numbers. This distribution is not equal and lower numbers are more likely to be detected compared to higher ones. In this investigation all numbers contained in the blinded abstracts of the 2009 annual meeting of the Swiss Society of Anesthesia and Resuscitation (SGAR) were recorded and analyzed regarding the distribution. A manipulated abstract was also included in the investigation. The χ(2)-test was used to determine statistical differences between expected and observed counts of numbers. There was also a faked abstract integrated in the investigation. A p<0.05 was considered significant. The distribution of the 1,800 numbers in the 77 submitted abstracts followed Benford's law. The manipulated abstract was detected by statistical means (difference in expected versus observed p<0.05). Statistics cannot prove whether the content is true or not but can give some serious hints to look into the details in such conspicuous material. These are the first results of a test for the distribution of numbers presented in medical research.

The occurrence of intra-operative hypotension varies between hospitals: observational analysis of over 147000 anaesthesia

Background: Hypotension, a common intra-operative incident, bears an important potential for morbidity. It is most often manageable and sometimes preventable, which renders its study important. Therefore, we aimed at examining hospital variations in the occurrence of intraoperative hypotension and its predictors. As secondary endpoints, we determined to what extent hypotension relates to the risk of postoperative incidents and death. Methods: We used the Anaesthesia Databank Switzerland, built on routinely and prospectively collected data on all anaesthesias in 21 hospitals. The three outcomes were assessed using multi-level logistic regression models. Results: Among 147573 anaesthesia, hypotension ranged from 0.6 to 5.2% in participating hospitals, and from 0.3 up to 12% in different surgical specialties. Most (73.4%) were minor single events. Age, ASA status, combined general and regional anaesthesia techniques, duration of surgery, and hospitalization were significantly associated to hypotension. Although significantly associated, the emergency status of the surgery had a weaker effect. Hospitals' Odds Ratios for hypotension varied between 0.12 to 2.50 (p ≤0.001) with respect to the mean prevalence of 3.1%, even after adjusting for patient and anaesthesia factors, and for type of surgery. At least one postoperative incident occurred in 9.7% of the interventions, including 0.03% deaths. Intra-operative hypotension was associated with higher risk of post-operative incidents and death. Conclusions: Wide variations in the occurrence of hypotension amongst hospitals remain after adjustment for risk factors. Although differential reporting from hospitals may exist, variations in anesthesia techniques and blood pressure maintenance could have also contributed. Intra-operative hypotension is associated with morbidities and sometimes death, and constant vigilance must thus be advocated.

Surgical treatment of ingrown toenail without matricectomy.

BACKGROUND: Partial excision of the nail matrix (matricectomy) is generally considered necessary in the surgical treatment of ingrown toenail. Recurrences may occur, however, and poor cosmetic results are frequently observed. OBJECTIVE: The objective is to present a new surgical procedure for ingrown toenail with complete preservation of the nail matrix. METHODS: Twenty-three patients with ingrown toenail were included in this study. The surgical excision was performed 1 week after the completion of treatment of the initial infection. A large volume of soft tissue surrounding the nail plate was removed under local anesthesia. No matrix excision was performed. RESULTS: Short-term results were excellent. No recurrences or severe complications were observed during the minimum 12-months follow-up period. Cosmetic results were remarkable. CONCLUSIONS: Ingrown toenail results from the compression of the lateral nail folds on the nail plate. This study shows that ingrown toenail can be surgically treated without matricectomy. A large volume of soft tissue surrounding the nail plate should be removed to decompress the nail and reduce inflammation. Cosmetic results are excellent and superior to the classical Emmert plasty. Postoperative nail dystrophies and spicule formation are not observed. The main advantage of this surgical approach is the complete preservation of the anatomy and function of the nail to improve both therapeutic and cosmetic results.

Evaluation of high frequency jet ventilation in patients undergoing percutaneous thermal ablation

Purpose: To evaluate the use of high frequency jet ventilation (HFJV) in patients undergoing percutanous thermal ablation procedures.Materials: From may to september 2011 patients with lung, liver or kidney tumors suitable for percutanous thermal ablation were prospectively enrolled to be treated under general anesthesia using HFJV instead of conventional positive pressure ventilation (PPV). Our primary endpoint was feasability of HFJV during percutanous ablation, our secondary endpoints were assessment of breathing related movements by image fusion (CT/US), precision and ease of needle placement by number of CT aquisition/needle reposition and procedure related complications.Results: Twenty-nine patients (21 males, 8 females mean age 66.2 years) with 30 liver tumors, 1 kidney tumors and 6 lung tumors were included. Tumor ablation was performed by radiofrequency (RFA) in 26 cases, microwaves ( MWA) in 2 and cryoablation (CRA) in 1. The ablation procedure could be completed under HFJV in 22 patients. In 2 patients HFVJ had to be stopped in favor of PPV because the tumor was better seen under PPV. HFJV was not performed in 5. Breathing related movements of the target lesion in the cranio-caudal direction as estimated by image fusion were always inferior to 5mm compared to 20mm when patients are under PPV. Needle placement was straightforward under CT as well as US. No patient needed needle repositionning before ablation. We did not observe any HFJV related complications.Conclusions: HFJV significantly reduces breathing movements of target lesion during percutaneous ablation procedures. It does not seem to cause any particular complication. However in some cases such as tumors located at the base of the lungs or in the dome of the liver, the target may be best seen under PPV.

Ultrasound-guided suprascapular nerve block, description of a novel supraclavicular approach.

BACKGROUND AND OBJECTIVES: The suprascapular nerve (SSN) block is frequently performed for different shoulder pain conditions and for perioperative and postoperative pain control after shoulder surgery. Blind and image-guided techniques have been described, all of which target the nerve within the supraspinous fossa or at the suprascapular notch. This classic target point is not always ideal when ultrasound (US) is used because it is located deep under the muscles, and hence the nerve is not always visible. Blocking the nerve in the supraclavicular region, where it passes underneath the omohyoid muscle, could be an attractive alternative. METHODS: In the first step, 60 volunteers were scanned with US, both in the supraclavicular and the classic target area. The visibility of the SSN in both regions was compared. In the second step, 20 needles were placed into or immediately next to the SSN in the supraclavicular region of 10 cadavers. The accuracy of needle placement was determined by injection of dye and following dissection. RESULTS: In the supraclavicular region of volunteers, the nerve was identified in 81% of examinations (95% confidence interval [CI], 74%-88%) and located at a median depth of 8 mm (interquartile range, 6-9 mm). Near the suprascapular notch (supraspinous fossa), the nerve was unambiguously identified in 36% of examinations (95% CI, 28%-44%) (P < 0.001) and located at a median depth of 35 mm (interquartile range, 31-38 mm; P < 0.001). In the cadaver investigation, the rate of correct needle placement of the supraclavicular approach was 95% (95% CI, 86%-100%). CONCLUSIONS: Visualization of the SSN with US is better in the supraclavicular region as compared with the supraspinous fossa. The anatomic dissections confirmed that our novel supraclavicular SSN block technique is accurate.

Management of refractory status epilepticus in adults: still more questions than answers.

Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite treatment with benzodiazepines and one antiepileptic drug. RSE should be treated promptly to prevent morbidity and mortality; however, scarce evidence is available to support the choice of specific treatments. Major independent outcome predictors are age (not modifiable) and cause (which should be actively targeted). Recent recommendations for adults suggest that the aggressiveness of treatment for RSE should be tailored to the clinical situation. To minimise intensive care unit-related complications, focal RSE without impairment of consciousness might initially be approached conservatively; conversely, early induction of pharmacological coma is advisable in generalised convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates are the most commonly used drugs. Several other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE. Treatment lasting weeks or months can sometimes result in a good outcome, as in selected patients after encephalitis or autoimmune disorders. Well designed prospective studies of RSE are urgently needed.

Sedación paliativa y sedación terminal : orientaciones para la toma de decisiones en la práctica clínica : documentos de apoyo

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Documento de Apoyo al Proceso Asistencial. Sedación Paliativa, Sedación Terminal)