Multimodal protocol for awake craniotomy in language cortex tumour surgery.

BACKGROUND: Intra-operative neurophysiological language mapping has become an established procedure in patients operated on for tumours in the area of the language cortex. Awake cranial surgery has specific risks and patients are exposed to an increased physical and mental stress. The aim of the study was to establish an algorithm that enables tailoring the neurosurgical and anaesthetic techniques to the individual patient. METHOD: A total of 25 patients underwent awake craniotomy for intra-operative language mapping between 1999 and 2004. Following craniotomy under analgesia and sedation without rigid pin fixation of the head, cortical language mapping was performed in the fully co-operative patient. The results of functional magnetic resonance imaging and of cortical language mapping were incorporated into the 3D dataset for neuronavigation. Depending on the functional data and the individual operative risk tumour resection then proceeded either under conscious sedation with the option of subcortical language monitoring or under general anaesthesia. FINDINGS: After cortical language mapping patients are assigned to one of four groups: BACC (Berlin awake craniotomy criteria) I-IV. BACC I (9 patients): adequate functional data+operative risk not increased-->tumour resection in the awake patient; BACC II (4 patients): limited functional data+operative risk not increased-->tumour resection in the awake patient with the option of language monitoring as needed; BACC III (9 patients): adequate functional data+increased operative risk-->tumour resection under general anaesthesia using functional navigation; BACC IV (3 patients): limited functional data+increased operative risk-->tumour resection in the awake patient with the option of language monitoring as needed. We observed less adverse events in group BACC III. No permanent deterioration of language function occurred in this series. CONCLUSIONS: The multimodal protocol for awake craniotomy provides for tumour resection under general anaesthesia in selected patients using functional neuronavigation. Our experience with the algorithm suggests that it is a useful tool for preserving function in patients undergoing surgery of the language cortex while reducing the operative risk on an individual basis.

High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes.

Lipopolysaccharide-binding protein (LBP), an acute-phase protein recognizing lipopolysaccharide (LPS), catalyzes in low concentrations its transfer to the cellular LPS receptor consisting of CD14 and Toll-like receptor-4. It has recently been shown that high concentrations of recombinant LBP can protect mice in a peritonitis model from the lethal effects of LPS. To determine whether in humans the acute-phase rise of LBP concentrations can inhibit LPS binding to monocytes and induction of proinflammatory cytokines, LBP concentrations were analyzed in 63 patients meeting the American College of Chest Physicians/Society of Critical Care Medicine criteria of severe sepsis or septic shock and the ability of these sera to modulate LPS effects in vitro was assessed employing different assays. Transfer of fluorescein isothiocyanate-labeled LPS to human monocytes was assessed by a fluorescence-activated cell sorter-based method, and activation of monocytes was investigated by measuring LPS-induced tumor necrosis factor-alpha secretion in the presence of the sera. Anti-LBP antibodies and recombinant human LBP were instrumental for depletion and reconstitution of acute-phase sera and subsequent assessment of their modulating effects on LPS activity. Sera of patients with severe sepsis/septic shock exhibited a diminished LPS transfer activity and LPS-induced tumor necrosis factor-alpha secretion as compared with sera from healthy controls. LBP depletion of sepsis sera and addition of rhLBP resulting in concentrations found in severe sepsis confirmed that LBP was the major serum component responsible for the observed effects. In summary, the inhibition of LPS effects by high concentrations of LBP in acute-phase serum, as described here, may represent a novel defense mechanism of the host in severe sepsis and during bacterial infections.

Transcranial Doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position.

BACKGROUND: Venous air embolism has been reported to occur in 23-45% of patients undergoing neurosurgical procedures in the sitting position. If venous air embolism occurs, a patent foramen ovale (PFO) is a risk factor for paradoxical air embolism and its sequelae. Preoperative screening for a PFO is therefore recommended by some investigators. The reference standard for identifying a PFO is contrast-enhanced transesophageal echocardiography (c-TEE). Contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) are noninvasive alternative methods, but so far there are no studies as to their diagnostic validity in neurosurgical patients. METHODS: The sensitivity and specificity of c-TCD and c-TTE in detecting a PFO were determined in a prospective study using c-TEE as the reference standard. Preoperative c-TCD, c-TTE, and c-TEE studies were performed during the Valsalva maneuver after intravenous echo-contrast medium (D-Galactose, Echovist-300, Schering AG, Berlin, Germany) was administered in 92 consecutive candidates (47 men and 45 women; mean age, 51 yr; range, 25-72 yr) before neurosurgical procedures in the sitting position. RESULTS: A PFO was detected in 24 of the 92 patients (26.0%) using c-TEE. c-TCD correctly identified 22 patients, whereas c-TTE only correctly identified 10. This corresponds to a sensitivity of 0.92 for c-TCD and 0.42 for c-TTE. The negative predictive value was 0.97 for c-TCD compared with 0.83 for c-TTE. The prevalence of a PFO in patients with a posterior fossa lesion was 27%, and in the group with cervical disc herniation was 24% as detected by c-TEE. The incidence of intraoperative venous air embolism was 35% in cases of cervical foraminotomy and 75% in posterior fossa surgery as detected by c-TEE. CONCLUSIONS: c-TCD is a highly sensitive and highly specific method for detecting a PFO. Because c-TCD is noninvasive, it may be more suitable than c-TEE for routine preoperative screening for a PFO. C-TTE is not reliable in detecting a PFO.

Interleukin-8 in urine: a new diagnostic parameter for intra-amniotic infection after premature rupture of the membranes.

Interleukin-8 (IL-8), a 72 amino acid peptide secreted by cells of the immune system and of the amnion, chorion and decidua, was measured in women in late pregnancy. IL-8 was detected in the urine of 91 of 104 women with premature rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of severe intra-amniotic infection. Women with urinary tract infections were excluded. The routine measurement of IL-8 in urine, together with C-reactive protein in serum, thus provides a low risk and technically simple approach to the assessment of intra-amniotic infection.

Epidemiology of invasive mycosis in ICU patients: a prospective multicenter study in 435 non-neutropenic patients. Paul-Ehrlich Society for Chemotherapy, Divisions of Mycology and Pneumonia Research.

OBJECTIVE: To determine the epidemiological and clinical significance of invasive fungal infections in non-neutropenic patients in intensive care who stay longer than 10 days on the intensive care unit (ICU). DESIGN: Prospective epidemiological multicenter study over a period of 11 months, based on strict clinical, bacteriological, serological and histological criteria. SETTING: Six surgical and two medical ICUs units in five university and two municipal hospitals. PATIENTS: 435 non-neutropenic patients from medical and surgical ICUs with an ICU stay of more than 10 days. MEASUREMENTS AND MAIN RESULTS: A new occurrence of invasive mycosis (3 sepsis/4 peritonitis/1 disseminated candidiasis), corresponding to the protocol conditions with onset after day 10 in the ICU, was detectable in 2.0% (95% confidence interval 0.85 to 3.8%) of the 409 patients who could be assessed. Candida species were identified as an infection-relevant pathogen in all cases. The most important risk factor for the development of an invasive mycosis was the onset of peritonitis by the day 11 in the ICU (odds ratio 11.3; p = 0.003). A fungal colonization was detected in 64% of patients (Candida species 56%, Aspergillus 4%, and other fungi). Six of 8 patients with an invasive mycosis died on the ICU; ICU mortality in patients with fungal colonization was 31% and in noncolonized patients 26%. Serological tests were not helpful clinically. The sensitivity was 88% for the Candida HAT (haemagglutination test) (threshold titer > 1:160), 100% for the Candida IFT (immunofluorescence test) (threshold titer > 1:80), and 50% for the Candida Antigen Test (Candtec Ramco, threshold titer > or = 1:8), and the specificity was 26, 6, and 73%, respectively. The specificity for the Aspergillus HAT (threshold titer > 1:10) was 29%. CONCLUSIONS: Invasive mycoses are rare in non-neutropenic ICU patients, even after a longer stay in the intensive care unit; fungal colonization, on the other hand, is frequently detectable. The mortality of invasive mycosis--even with systemic antimycotic therapy--was high; the mortality in patients with fungal colonization was not significantly increased compared to that in noncolonized patients. The serological test procedures, Candida HAT, Candida IFT, and the Candida Ramco Antigen Test, had a low specificity and were not helpful in diagnosing relevant invasive mycosis.

[Importance and physiologic nutritional requirement of the selenium trace element within the scope of parenteral nutrition (TPN)]. / Bedeutung und ernährungsphysiologischer Bedarf des Spurenelementes Selen im Rahmen der parenteralen Ernährung (TPN).

BASIS: Selenium-responsive clinical manifestations of selenium deficiency and elucidation of the biochemical and molecular biological basis of the essentiality of selenium give evidence for the biological importance of the trace element in human nutrition. CONCLUSION: The dietary parenteral selenium requirement can be calculated on the basis of the maximal gene expression of the selenoprotein plasma glutathione peroxidase (plGPx). In total parenteral nutrition a daily requirement of 0.01 mumol/kg body weight for adults and 0.025 mumol/kg body weight for children can be seen as adequate and safe.

[Intubation trauma of the larynx--a literature review with special reference to arytenoid cartilage dislocation]. / Intubationstraumen des Larynx--eine Literaturübersicht unter besonderer Berücksichtigung der Aryknorpelluxation.

Trauma to the cricoarytenoid joint represents a rare but serious complication of endotracheal intubation. Subluxation and luxation of the arytenoid cartilage may occur during difficult but also following uncomplicated intubation. Forces on the arytenoid cartilage exerted by the laryngoscope blade or by the distal part of the endotracheal tube may cause anterior and inferior displacement of the arytenoid cartilage. Due to the conventional intubation technique the left arytenoid cartilage is affected most frequently. Posterolateral subluxation is attributed to the pressure exerted on the posterior glottis by the convex part of the shaft of the tube. Systemic diseases (e.g. terminal renal insufficiency, bowel diseases, acromegaly) may cause degeneration of the cricoarytenoid ligaments, thus making the cricoarytenoid joint more susceptible to traumatic dislocation. Persisting alterations of voice, sore throat and pain on swallowing may hint to the diagnosis of arytenoid dislocation. However, stridor and shortness of breath have also been observed. If pharyngo-laryngeal complaints persist, evaluation by laryngologists is mandatory. In addition to indirect and direct laryngoscopy, computerised tomography and electromyography of the larynx play an important role in differentiating arytenoid dislocation from true vocal cord paralysis due to nerve damage. Early operative reposition results in fair prognosis, whereas delayed diagnosis may lead to ankylosis of the cricoarytenoid joint with permanent impairment of the voice and possibly compromised airway protection.

The necessity of selenium substitution in total parenteral nutrition and artificial alimentation.

For the trace element selenium, in contrast to zinc, iron, copper, chromium, manganese and iodine, there is still no clear official recommendation with regard to routine substitution in artificial nutrition. An overview of the manifestations of selenium deficiency in humans during the period 1979-1995 shows that nutritive deficiencies are exclusively TPN-induced or the result of severe malnutrition. The pathology of TPN-induced selenium deficiency and the analytic assessment of selenium status are described. Patients undergoing long-term parenteral nutrition or suffering from an increased loss of intestinal secretions have to be characterized as being especially at risk for clinical selenium deficiency. The relationship of the serum selenium kinetics in pediatric and adult patients to the depletion of body compartments during the course of short-term and prolonged TPN is discussed. Because of the importance of the selenoproteins, the regularly occurring depletion during selenium-free TPN and the borderline supply of selenium in Germany the routine substitution of selenium in TPN is strongly recommended. The pharmaceutical industry should be encouraged to develop a trace element solution that includes selenium, so that the nutritive requirement of patients on TPN can be satisfied. Adequate intravenous dosage recommendations are based on maintenance of glutathione peroxidase homeostasis. The routine supplementation dosage may not meet the selenium requirements of intensive care patients under conditions of increased metabolic demands on their anti-oxidative system.

Parenteral aluminum loading in critical care medicine. Part II: Response to aluminum load from long-term parenteral nutrition.

OBJECTIVE: Evaluation of the iatrogenic aluminum load by aluminum-contaminated nutritive infusion solutions in long-term total parenteral nutrition (TPN). PATIENTS: 16 consecutive patients (6 children, 10 adults) who had to undergo total parenteral nutrition for more than one month. Three of them were from a home parenteral nutrition program. The duration of TPN was up to 68 months. The parenteral aluminum load was calculated on the basis of the individual TPN programs. Six patients were exposed to an additional parenteral aluminum load in the course of intensive care. Comparative group: To establish a reference range, the serum aluminum concentrations were determined in 71 unloaded patients who had to undergo minor surgical procedures. ALUMINUM ANALYSIS: Strict adherence to a contamination-free sampling and processing technique. The aluminum determination was performed at the Hahn-Meitner-Institute Berlin by means of graphite-furnace atomic absorption spectrometry (GFAAS). RESULTS: The TPN-associated daily aluminum load was 3.5 +/- 0.4 micrograms/kg body weight (bw) in children and 2.2 +/- 1.8 micrograms/kg bw in adults. 59 +/- 6% of the intravenous aluminum load in children and 42 +/- 16% in adults was due to the highly contaminated small-volume calcium, inorganic phosphate, trace element and vitamin parenterals. The median serum aluminum concentration under TPN was 10.9 micrograms/l (range: 5.0-26.9 micrograms/l) and was thus 7.3 times higher than in the preoperative control group (median: 1.5 micrograms/l, 95% confidence interval: < 0.6-3.5 micrograms/l). Individual values ranged up to 36.8 micrograms/l. CONCLUSIONS: The aluminum intake of patients on parenteral nutrition in Germany is thus on occasion considerably above the ASCN/ASPEN recommendations for the limitation of intravenous aluminum loading (ASCN: American Society for Clinical Nutrition; ASPEN: American Society for Parenteral and Enteral Nutrition). The toxicological significance of parenteral aluminum loading is discussed. The results suggest that limits should be established for the Aluminum contamination of infusion solutions.

Parenteral aluminum loading in critical care medicine. Part I: Aluminum content of infusion solutions and solutions for parenteral nutrition.

BACKGROUND: For patients with disturbed aluminum (Al) excretion, a high Al intake is not without risk. As main aluminum sources infusion solutions and solutions for parenteral nutrition have been identified. This study will give current survey of aluminum loading of the above-mentioned preparations. MATERIAL AND METHODS: The aluminum loading of 139 different infusion solutions and solutions for parenteral nutrition was determined. The solutions were from the clinical pharmacy of the Klinikum Steglitz of the Free University Berlin or were bought in a public pharmacy. The aluminum content was determined by means of two different, independent analytical methods: a) graphite furnace atomic absorption spectroscopy (GFAAS) and b) inductively coupled plasma atomic emission spectroscopy (ICP-AES). The agreement of the measured values was good except for five samples, where different values were found. Mistakes due to contamination were excluded on the basis of the results of measuring standard reference materials. RESULTS: Small-volume additives of TPN (total parenteral nutrition) formulations were highly contaminated with aluminum, e.g. Ca and phosphate solutions (29-12,000 micrograms/l), vitamin C solutions (700-1,200 micrograms/l) and trace element solutions (67-6,200 micrograms/l). Furthermore about 44% of the crystalline amino acid solutions and lipid emulsions had an aluminum content of 25 to 55 micrograms/l. Low aluminum levels were found in carbohydrate solutions, NaCl and KCl solutions and in distilled water (aqua ad injectabilia). CONCLUSIONS: Many of the solutions for parenteral nutritional support have an aluminum content which exceeds, in part considerably, the suggested threshold concentration of 25 micrograms/l (0.93 mumol/l), recommended by the American Society for Clinical Nutrition (ASCN) and the American Society for Parenteral and Enteral Nutrition (ASPEN). The pharmaceutical industry should be required to check the manufacturing process for avoidable sources of contamination, and threshold values for aluminum loading by intravenously applied pharmaceuticals should be laid down in the German and European pharmacopoeia. In cases where contaminations cannot be eliminated during the manufacturing process after careful checking, the aluminum content of the infusion solution should be declared for the user.

The kinetics of metamizol and its metabolites in critical-care patients with acute renal dysfunction.

We have studied the clearance of monomethylaminoantipyrine (MMAAP), the pharmacologically active form of metamizol, in 46 patients in surgical intensive care with different degrees of renal dysfunction. In 23 patients without any renal impairment, mean clearance was 2.8 ml.min-1 x kg-1. Twenty-one patients with acute renal impairment had a significantly reduced clearance of MMAAP (0.83 ml.min-1 x kg-1). There was also reduced clearance in four patients with septic shock (1.0 ml.min-1 x kg-1). Kinetics of the metabolites of MMAAP (N-formylaminoantipyrine (FAAP), aminoantipyrine (AAP), and its secondary product N-acetylaminoantipyrine (AcAAP)) were calculated. FAAP and AcAAP showed delayed invasion, which can be explained by reduced hepatic metabolic activity. The product of N-demethylation, AAP, was not significantly altered. The delayed elimination of monomethylaminoantipyrine can be explained by reduced hepatic function in parallel with acute renal failure due to disturbed cardiovascular function caused by septic shock. This may also lead to disturbed hepatic macro- and microperfusion associated with altered oxygen supply and oxygen consumption.

[Irreversible valproate-associated liver failure]. / Irreversibles valproatassoziiertes Leberversagen.

A very severely retarded infant with a Dandy-Walker malformation was treated with valproate since the age of 6 months on account of infantile spasms. Three weeks after start of therapy dexamethasone was applied additionally because valproate was ineffective. Seventy-six days after initiation of valproate therapy the infant died with the clinical signs of fulminant valproate-associated hepatotoxicity despite the discontinuation of valproate. In combination with a febrile otitis media the child had been periodically restless and lethargic during the last week prior to liver coma. Activity of liver enzymes remained within normal limits up to two days before coma occurred. Analysis of valproate metabolites by gas chromatography/mass spectrometry yielded unusually high concentrations of the di-unsaturated metabolite E,E-2,3'-dien-valproate before and during liver failure. The concentrations of the main metabolites E-2-en-valproate und 3-keto-valproate remained within the usual range found during valproate therapy at steady state. The oxydation products 4-en-valproate and E-2,4-dien-valproate which are formed by alternative pathways and are considered to be hepatotoxic were detected in very low concentrations only. The application of carnitine, of antioxidants thought to improve the capacity of the free radical scavenger system (selen, vitamin E), and of N-acetylcysteine which can detoxify reactive drug metabolites could not prevent the fatal outcome.