[Vibrio vulnificus, an increasing threat of sepsis in Germany?] / Vibrio vulnificus, eine zunehmende Sepsisgefahr in Deutschland?

BACKGROUND: The prevalence of Vibrio vulnificus heavily depends on the temperature and salinity of the sea water. In the course of climate change an increase in cases of fatal sepsis caused by V. vulnificus at the German Baltic Sea coast could be detected. OBJECTIVE: To generate awareness for a life-threatening infection with increasing incidence in Germany. MATERIAL AND METHODS: This article presents an overview of the current state of the literature followed by an exemplary description of cases with V vulnificus sepsis caused by contact with water in the Baltic Sea, which were treated at the Medical University in Greifswald in summer 2018. RESULTS: In the presence of risk factors, such as liver and kidney diseases, immunosuppression and male sex, there is a danger of severe sepsis if damaged skin comes into contact with contaminated sea water. A pronounced organ dysfunction can frequently be found on admission. In these cases the diagnosis must be made promptly and timely surgical cleansing and antibiotic treatment should be initiated (e.g. a combination of tetracyclines and third generation cephalosporins). CONCLUSION: Sepsis due to V. vulnificus will probably increase over the coming years. Because there is a latency in some cases between infection and onset of sepsis, physicians beyond the coastal region must also be informed about this disease.

Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

OBJECTIVES: Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy. METHODS: Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity. RESULTS: In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy. CONCLUSIONS: Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

[Therapy escalation for the potential organ donor : Are all intensive care measures also ethically justifiable?] / Therapieeskalation beim potenziellen Organspender : Sind alle intensivmedizinischen Maßnahmen auch ethisch zu rechtfertigen?

The gap between the number of organs needed and the number available has dramatically increased in Germany in the last decade-for intensivists and transplantation specialists, it is challenging to cover the demand responsibly. It is therefore increasingly important to identify potential organ donors in order to realize organ donation. An escalation of intensive care measures is often required, which raises critical ethical questions. In Germany, organ donation is only allowed after brain death with prior informed consent from the deceased or his/her relatives. Determining the willingness of the potential organ donor and adapting the subsequent intensive care to it requires experience and empathy. Therapy escalation for the realization of organ donation is not opposed to the basic ethical principles of medicine, but remains an individual decision. A time limitation of this last intensive therapy phase to achieve optimal conditions for transplantation should be discussed with the relatives and adapted to the medical requirements. This article would like to highlight ethical questions that are relevant in the context of therapy escalation of potential organ donors and, thus, support the decision-making process.

[Critical care management of the potential organ donor : Current recommendation for adults]. / Intensivmedizinisches Management des potentiellen Organspenders : Aktuelle Empfehlungen für Erwachsene.

The shortage of donor organs has not improved in recent years. To increase the number and success of transplantation it is crucial to optimize the processes of early identification of potential organ donors and structured critical care management. The therapy starts long before brain death is diagnosed. Structured in-house organ donor management protocols ensure a highly qualified critical care that has a direct impact on the transplantation outcome. The therapy is based on the established standards. The main focus is on differentiated catecholamine and volume therapy. Vasopressin, in combination with norepinephrine, is effective for both treating vasoplegia and electrolyte disturbances. Despite poor evidence, steroids are useful for stabilizing hemodynamics and treating the consequences of neuroendocrine dysfunction. Overall, prospective studies are required to give general recommendations for critical care.

[Sepsis detection in emergency medicine : Results of an interprofessional survey on sepsis detection in prehospital emergency medicine and emergency departments]. / Sepsis erkennen im Rettungsdienst : Ergebnisse einer interprofessionellen Befragung zur präklinischen und frühen innerklinischen Sepsiserkennung.

BACKGROUND: Sepsis is associated with a high mortality, which can be reduced by starting screening, diagnostics and treatment as early as possible. Due to multiple educational programs and increased awareness, a decreased sepsis mortality on intensive care units has been achieved. Many patients with sepsis are admitted by the prehospital emergency service to hospital emergency departments. Thus, prehospital emergency services and emergency departments provide an opportunity to start screening, diagnosis and treatment earlier. OBJECTIVES: To detect sepsis it is paramount that emergency personnel are aware of the disease and have a profound knowledge regarding symptoms, screening and diagnostics. The objective of this survey was to examine the state of knowledge regarding sepsis among staff working in emergency medicine. MATERIAL AND METHODS: To assess the awareness and knowledge, a paper-based, anonymous survey was conducted among prehospital and emergency department personnel from May to August 2017 in northeastern Germany. Testing of significance was carried out using the χ2-testand Fisher's exact test. RESULTS: Out of 411 persons polled 212 answered (response rate 51.6%) and 24 questionnaires were incomplete and thus excluded. A total of 188 questionnaires were included covering 55 emergency physicians, 23 nurses, 82 paramedics and 19 emergency dispatchers. On a 4-point Likert scale 100% of emergency doctors, 96% of nurses, 84% of paramedics and 84% of emergency dispatchers considered early initiation of sepsis treatment to be important. Additionally, 92% of emergency physicians and 65% of nurses had attended educational programs on sepsis within the last year, which is significantly higher than among paramedics (19%, p < 0.01) and emergency dispatchers (21%, p = 0.025). In addition, 38% of paramedics and 47% of emergency dispatchers had never attended lectures on sepsis. The quick sequential (sepsis-related) organ failure assessment (qSOFA) was known by 80% of emergency doctors, thus, significantly more often than by nurses (26%), paramedics (29%) and emergency dispatchers (29%, p < 0.01). The emergency personnel were asked to tick all symptoms they associated with sepsis from a display of 14 symptoms. Among all occupation groups the majority selected "increased body temperature", "drop in blood pressure" and "altered breathing". In relation to "increased body temperature" the symptom "altered mental status" was selected significantly more frequently by emergency doctors than by nurses and paramedics (p = 0.02 and p < 0.01, respectively). The combination of at least all 3 qSOFA parameters was selected significantly more often by emergency doctors (62%) than by nurses (13%) and paramedics (10%, p = 0.017 and p < 0.01, respectively). CONCLUSION: Although emergency personnel rated an early initiation of sepsis treatment as important, sepsis knowledge was limited. While the majority of emergency doctors and many nurses had attended educational programs on sepsis within the last year, an alarmingly high percentage of paramedics and emergency dispatchers had never received sepsis education. Emergency personnel are mostly unfamiliar with the qSOFA score and did not associate an altered mental status with sepsis. In light of the high sepsis morbidity and mortality, further achievements might be made by initiating sepsis screening and diagnostics in the prehospital setting. Analogous to advancements in intensive care units, increased educational programs for emergency personnel might lead to an earlier detection and improved prognosis of sepsis.

Bystander-witnessed cardiac arrest is associated with reported agonal breathing and leads to less frequent bystander CPR.

AIM: Although the importance of bystander cardiopulmonary resuscitation has been shown in multiple studies, the rate of bystander cardiopulmonary resuscitation is still relatively low in many countries. Little is known on bystanders' perceptions influencing the decision to start cardiopulmonary resuscitation. Our study aims to determine such factors. MATERIALS AND METHODS: Semi-structured telephone interviews with bystanders of out-of-hospital cardiac arrests between December 2014 and April 2016 were performed in a prospective manner. This single-center survey was conducted in the city of Münster, Germany. The bystander's sex and age, the perception of the victim's breathing and initial condition were correlated with the share of bystander cardiopulmonary resuscitation in the corresponding group. RESULTS: 101 telephone interviews were performed with 57 male and 44 female participants showing a mean age of 52.7 (SD ±â€¯16.3). In case of apnoea 38 out of 46 bystanders (82.6%) started cardiopulmonary resuscitation; while in case of descriptions indicating agonal breathing 19 out of 35 bystanders (54.3%) started cardiopulmonary resuscitation (p = .007). If the patient was found unconscious 47 out of 63 bystanders (74.7%) performed cardiopulmonary resuscitation, while in cases of witnessed cardiac arrest 19 out of 38 bystanders (50%) attempted cardiopulmonary resuscitation (p = .012). Witnessed change of consciousness is an independent factor significantly lowering the probability of starting cardiopulmonary resuscitation (regression coefficient -1.489, p < .05). CONCLUSION: The witnessed loss of consciousness was independently associated with a significant reduction in the likelihood that bystander-CPR was started. These data reinforce the importance of teaching the recognition of early cardiac arrest.

Continuing chronic beta-blockade in the acute phase of severe sepsis and septic shock is associated with decreased mortality rates up to 90 days.

BACKGROUND: There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock. METHODS: The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade. RESULTS: A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03). CONCLUSIONS: Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.

Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis.

BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty-five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery.

Time-dependent modulation of muscarinic m1/m3 receptor signalling by local anaesthetics.

BACKGROUND: Signalling of several G-protein-coupled receptors of the Gq/11 family is time-dependently inhibited by local anaesthetics (LAs). Since LA-induced modulation of muscarinic m1 and m3 receptor function may explain their beneficial effects in clinical practice, such as decreased postoperative cognitive dysfunction or less bronchoconstriction, we studied how prolonged exposure affects muscarinic signalling (Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg 2002; 95: 1134-41; Groeben H, Silvanus MT, Beste M, Peters J. Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction. Chest 2000; 118: 509-15). METHODS: A two-electrode voltage clamp was used to assess the effects of lidocaine or its permanently charged analogue QX314 on recombinantly expressed m1 and m3 receptors in Xenopus oocytes. Antisense knock-down of functional Gαq-protein and inhibition of protein kinase C (PKC) served to define mechanisms and sites of action. RESULTS: Lidocaine affected muscarinic signalling in a biphasic way: an initial decrease in methylcholine bromide-elicited m1 and m3 responses after 30 min, followed by a significant increase in muscarinic responses after 8 h. Intracellularly injected QX314 time-dependently inhibited muscarinic signalling, but had no effect in Gαq-depleted oocytes. PKC-antagonism enhanced m1 and m3 signalling, but completely abolished the LA-induced increase in muscarinic responses, unmasking an underlying time-dependent inhibition of m1 and m3 responses after 8 h. CONCLUSIONS: Lidocaine modulates muscarinic m1 and m3 receptors in a time- and Gαq-dependent manner, but this is masked by enhanced PKC activity. The biphasic time course may be due to interactions of LAs with an extracellular receptor domain, modulated by PKC activity. Prolonged exposure to LAs may not benefit pulmonary function, but may positively affect postoperative cognitive function.

Anesthetic management in pediatric patients with epidermolysis bullosa: a single center experience.

BACKGROUND: Anesthesia in children with dystrophic epidermolysis bullosa (EB) presents a significant challenge as many children have a difficult airway and are at risk for additional blistering. In this retrospective study we compared deep sedation/ analgesia and general anesthesia for safety and efficiency. Procedure, type of anesthesia, airway management, complications, time for induction and awakening, length of stay in recovery room, length of procedure were noted and compared, qualitatively and with statistic tests as appropriate. METHODS: Fourteen children underwent 148 procedures: 79 under general anesthesia, 67 under sedation. RESULTS: Several complications - including intubation difficulties and the need for change of airway management - were observed in the general anesthesia group, none in the sedated group. Induction time was 36 min vs. 17 min (P<0.001), mean time to recovery 23 min vs. 6 min (P<0.001). Surgical duration did not differ between groups. CONCLUSIONS: In children with dystrophic EB deep sedation/ analgesia can be safely performed and is less time consuming than traditional management.

Ultrasound-guided axillary plexus block in a child with dystrophic epidermolysis bullosa.

We report the use of ultrasound-guided axillary brachial plexus block in a child with dystrophic epidermolysis bullosa needing surgical treatment of the right hand. The regional anaesthesia was used in association with sedation/ anaesthesia. This technique is suitable for these difficult patients because it can minimise the risk of new bullae formation due to palpation of landmarks or unintentional intra- or subcutaneous injections. Initial anaesthesia/sedation was provided with sevoflurane until intravenous access was obtained, following which intravenous propofol infusion with ketamine boluses without any invasive airway management was continued for performance of the block and the procedure. This management plan provided good surgical conditions, early postoperative analgesia, minimised stress for the patient and avoided the need to manipulate the airway with instruments and the associated risk of mucosal bullae. The classification and breadth of clinical manifestation of epidermolysis bullosa is complex and briefly summarised. The anaesthetist should clarify the details of a particular patient's form of epidermolysis bullosa, especially in terms of mucosal involvement, as this may greatly influence planning for a procedure.

Local anaesthetics inhibit signalling of human NMDA receptors recombinantly expressed in Xenopus laevis oocytes: role of protein kinase C.

BACKGROUND: N-methyl-D-aspartate (NMDA)-receptor activation contributes to postoperative hyperalgesia. Studies in volunteers have shown that intravenous local anaesthetics (LAs) prevent the development of hyperalgesic pain states. One potential explanation for this beneficial effect is the inhibition of NMDA receptor activation. Therefore, we studied the effects of LA on NMDA receptor function. METHODS: The human NR1A/NR2A NMDA receptor was expressed recombinantly in Xenopus laevis oocytes. Peak currents were measured by voltage clamp in Mg- and Ca2+-free, Ba2+-containing Tyrode's solution. Holding potential was -70 mV. Oocytes were stimulated with glutamate/glycine (at EC50) with or without 10 min prior incubation in bupivacaine, levobupivacaine, S-(-)-ropivacaine, or lidocaine (all at 10(-9)-10(-4) M), procaine (10(-4) M), R-(+)-ropivacaine (10(-4) M), QX314 (permanently charged, 5 x 10(-4) M) extracellularly or intracellularly or benzocaine (permanently uncharged, 5 x 10(-3) M). We also determined the effect of the protein kinase C (PKC) inhibitors chelerythrine (5 x 10(-5) M), calphostin C (3 x 10(-6) M) and Ro 31-8220 (10(-7) M), and the effect of PKC activation with phorbolester (10(-6) M). RESULTS: Non-injected oocytes were unresponsive to agonist application, but oocytes expressing NMDA receptors responded with inward currents (1.1+/-0.08 microA). All LA concentration-dependently inhibited agonist responses. The inhibition was reversible and stereoselective. Intracellular QX314 reduced responses to 59% of control, but extracellular QX314 was without effect. Benzocaine reduced responses to 33% of control. PKC inhibitors had no additional inhibitory effect beyond that of bupivacaine. The effect of PKC activation was abolished in the presence of bupivacaine. CONCLUSION: All LA tested inhibited the activation of human NMDA receptors in a concentration dependent fashion. This effect may contribute to reduced hyperalgesia and opiate tolerance observed after systemic administration of LA. The effect is independent of the charge of LA; site of action is intracellular. The mechanism of action may be mediated by inhibition of PKC.

The inhibitory effect of bupivacaine on prostaglandin E(2) (EP(1)) receptor functioning: mechanism of action.

Prostaglandin E(2) receptors, subtype EP(1) (PGE(2)EP(1)) have been linked to several physiologic responses, such as fever, inflammation, and mechanical hyperalgesia. Local anesthetics modulate these responses, which may be due to direct interaction of local anesthetics with PGE(2)EP(1) receptor signaling. We sought to characterize the local anesthetic effects on PGE(2)EP(1) signaling and elucidate mechanisms of anesthetic action. In Xenopus laevis oocytes, recombinant expressed PGE(2)EP(1) receptors were functional (half maximal effect concentration, 2.09 +/- 0.98 x 10(-6) M). Bupivacaine, after incubation for 10 min, inhibited concentration-dependent PGE(2)EP(1) receptor functioning (half-maximal inhibitory effect concentration, 3.06 +/- 1.26 x 10(-6) M). Prolonged incubation in bupivacaine (24 h) inhibited PGE(2)-induced calcium-dependent chloride currents (I(Cl(Ca))) even more. Intracellular pathways were not significantly inhibited after 10 min of incubation in bupivacaine. But I(Cl(Ca)) activated by intracellular injection of GTPgammaS (a nonhydrolyzable guanosine triphosphate [GTP] analog that activates G proteins, irreversible because it cannot be dephosphorylated by the intrinsic GTPase activity of the alpha subunit of the G protein) was reduced after 24 h of incubation in bupivacaine, indicating a G protein-dependent effect. However, inositol 1,4,5-trisphosphate- and CaCl(2)- induced I(Cl(Ca)) were unaffected by bupivacaine at any time points tested. Therefore, bupivacaine's effect is at phospholipase C or at the G protein or the PGE(2)EP(1) receptor. All inhibitory effects were reversible. We conclude that bupivacaine inhibited PGE(2)EP(1) receptor signaling at clinically relevant concentrations. These effects could, at least in part, explain how local anesthetics affect physiologic responses such as fever, inflammation, and hyperalgesia during the perioperative period.

Minimal-flow anaesthesia with controlled ventilation: comparison between laryngeal mask airway and endotracheal tube.

BACKGROUND AND OBJECTIVE: Minimal- and low-flow anaesthesia (fresh gas flow below 1 L min(-1)) provide many advantages, including reduced cost, conservation of body heat and airway humidity. An airtight seal is essential between the airway device and the airway of the patient. Therefore, we investigated whether the airtight seal created by a laryngeal mask airway allows controlled ventilation of the lungs when the fresh gas flow is reduced to 0.5 L min(-1) and compared this with an endotracheal tube. METHODS: In a prospective clinical study, 207 patients were managed using a laryngeal mask or an endotracheal tube. After intravenous induction of anaesthesia and 15 min of high fresh gas flow, the flow was reduced to 0.5 L min(-1). The breathing system was monitored for airway leaks, and the patients were assessed for complications after airway removal and postoperative discomfort. RESULTS: Both the laryngeal mask and endotracheal tube allowed fresh gas flow reduction to 0.5 L min(-1) in 84.7% and 98.3% of cases respectively (small leaks: 12% laryngeal mask, 1.7% endotracheal tube). Three patients with the laryngeal mask (3.3%) had airway leaks that were too large to permit any reduction in the fresh gas flow. CONCLUSIONS: The use of the laryngeal mask airway was more likely to be associated with a gas leak than use of an endotracheal tube; however, if modern anaesthesia machines and monitors are used, in 96.7% of the patients managed with a laryngeal mask a reduction in the fresh gas flow to 0.5 L min(-1) was possible. The incidence of coughing and postoperative complaints (sore throat, swallowing problems) was higher after use of an endotracheal tube.

Selective iNOS inhibition prevents hypotension in septic rats while preserving endothelium-dependent vasodilation.

UNLABELLED: Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) mediates hypotension and metabolic derangements in sepsis. We hypothesized that selective iNOS-inhibition would prevent hypotension in septic rats without inhibiting endothelium-dependent vasodilation caused by the physiologically important endothelial NOS. Rats were exposed to lipopolysaccharide (LPS) for 6 h and the selective iNOS-inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL), the nonselective NOS-inhibitor N:(G)-nitro-L-arginine methyl ester (L-NAME), or control. Mean arterial pressure (MAP) and vasodilation to acetylcholine (ACh, endothelium-dependent), sodium nitroprusside (SNP, endothelium-independent), and isoproterenol (ISO, endothelium-independent beta agonist) were determined. Exhaled NO, nitrate/nitrite-(NOx) levels, metabolic data, and immunohistochemical staining for nitrotyrosine, a tracer of peroxynitrite-formation were also determined. In control rats, L-NAME increased MAP, decreased the response to ACh, and increased the response to SNP, whereas L-NIL did not alter these variables. LPS decreased MAP by 18% +/- 1%, decreased vasodilation (ACh, SNP, and ISO), increased exhaled NO, NOx, nitrotyrosine staining, and caused acidosis and hypoglycemia. L-NIL restored MAP and vasodilation (ACh, SNP, and ISO) to baseline and prevented the changes in exhaled NO, NOx, pH, and glucose levels. In contrast, L-NAME restored MAP and SNP vasodilation, but did not alter the decreased response to ACh and ISO or prevent the changes in exhaled NO and glucose levels. Finally, L-NIL but not L-NAME decreased nitrotyrosine staining in LPS rats. In conclusion, L-NIL prevents hypotension and metabolic derangements in septic rats without affecting endothelium-dependent vasodilation whereas L-NAME does not. IMPLICATIONS: Sepsis causes hypotension and metabolic derangements partly because of increased nitric oxide. Selective inhibition of nitric oxide produced by the inducible nitric oxide synthase enzyme prevents hypotension and attenuates metabolic derangements while preserving the important vascular function associated with endothelium-dependent vasodilation in septic rats.

Effect of different anaesthetic regimes on the oculocardiac reflex during paediatric strabismus surgery.

The oculocardiac reflex (OCR) is induced by mechanical stimulation and therefore is frequently encountered during strabismus surgery. This study was designed to determine how various anaesthetic regimes modulate the haemodynamic effects of the OCR during paediatric strabismus surgery. Thirty-nine patients (4-14 years, ASA I) were randomized to one of four anaesthetic regimes: group P: propofol (12 mg.kg(-1).h(-1)) and alfentanil (0.04 mg.kg(-1).h(-1)); group S: sevoflurane 1-1.2 MAC in 30% O(2)/70% N(2)O; group K: ketamine racemate (10-12 mg. kg(-1).h(-1)) and midazolam (0.3-0.6 mg.kg(-1).h(-1); group H: halothane 1-1. 2 MAC in 30% O(2)/70% N(2)O. Electrocardiogram (ECG), beat-to-beat heart rate (HR) and blood pressure (BP) changes were measured during and after a standardized traction was applied to an external eye muscle (4-6 Newton, 90 s). OCR was defined as a 10% change in HR induced by traction. OCR occurred in 77% of patients. Whereas virtually all patients in the P, H and S groups developed OCR, only 22% developed it in group K. Median HR change in group P (-37 bpm) was significantly greater (P < 0.05) than in group H (-17 bpm) or group K (-7 bpm). Median BP change in group K (+10 mmHg) was significantly different (P < 0.05) from group H (-5 mmHg), group S (-3 mmHg) and group P (-8 mmHg). Atrioventricular rhythm disorders were significantly more frequent in group P compared with group K (P < 0.02). Respiration-induced sinus dysrhythmia was significantly less frequent (P < 0.001) in group K (0%), compared with group P (100%), group H (56%) and group S (55%). Of the anaesthetic techniques studied, ketamine anaesthesia is associated with the least haemodynamic changes induced by OCR during strabismus surgery in paediatric patients.

Selective iNOS inhibition attenuates acetylcholine- and bradykinin-induced vasoconstriction in lipopolysaccharide-exposed rat lungs.

BACKGROUND: Nonselective nitric oxide synthase (NOS) inhibition has detrimental effects in sepsis because of inhibition of the physiologically important endothelial NOS (eNOS). The authors hypothesized that selective inducible NOS (iNOS) inhibition would maintain eNOS vasodilation but prevent acetylcholine- and bradykinin-mediated vasoconstriction caused by lipopolysaccharide-induced endothelial dysfunction. METHODS: Rats were administered intraperitoneal lipopolysaccharide (15 mg/kg) with and without the selective iNOS inhibitors L-N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg), dexamethasone (1 mg/kg), or the nonselective NOS inhibitor Nomega-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Six hours later, the lungs were isolated and pulmonary vasoreactivity was assessed with hypoxic vasoconstrictions (3% O2), acetylcholine (1 microg), Biochemical Engineering, and bradykinin (3 microg). In additional lipopolysaccharide experiments, L-NIL (10 microM) or 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 100 microM), a selective muscarinic M3 antagonist, was added into the perfusate. RESULTS: Exhaled nitric oxide was higher in the lipopolysaccharide group (37.7+/-17.8 ppb) compared with the control group (0.4+/-0.7 ppb). L-NIL and dexamethasone decreased exhaled nitric oxide in lipopolysaccharide rats by 83 and 79%, respectively, whereas L-NAME had no effect. In control lungs, L-NAME significantly decreased acetylcholine- and bradykinin-induced vasodilation by 75% and increased hypoxic vasoconstrictions, whereas L-NIL and dexamethasone had no effect. In lipopolysaccharide lungs, acetylcholine and bradykinin both transiently increased the pulmonary artery pressure by 8.4+/-2.0 mmHg and 35.3+/-11.7 mmHg, respectively, immediately after vasodilation. L-NIL and dexamethasone both attenuated this vasoconstriction by 70%, whereas L-NAME did not. The acetylcholine vasoconstriction was dose-dependent (0.01-1.0 microg), unaffected by L-NIL added to the perfusate, and abolished by 4-DAMP. CONCLUSIONS: In isolated perfused lungs, acetylcholine and bradykinin caused vasoconstriction in lipopolysaccharide-treated rats. This vasoconstriction was attenuated by administration of the iNOS inhibitor L-NIL but not with L-NAME. Furthermore, L-NIL administered with lipopolysaccharide preserved endothelium nitric oxide-dependent vasodilation, whereas L-NAME did not.

[Can sevoflurane save time in routine clincal use? A comparison with halothane in pediatric anesthesia]. / Kann Sevofluran im klinischen Alltag den zeitlichen Ablauf beschleunigen? Ein Vergleich mit Halothan bei Kinderanästhesien.

UNLABELLED: The volatile agent sevoflurane enables a rapid emergence from anaesthesia. The aim of this study was to investigate the possibility of increasing turnover in pediatric anaesthetic cases by use of sevoflurane in comparison with halothane. Often short cases or day cases need rapid turnover. METHODS AND PATIENTS: The pediatric patients aged 4-14 years (ASA I) presenting for elective ophthalmic surgery were randomised to either the halothane or the sevoflurane group. Standard monitoring was applied to all patients, in addition the pEEG was used to determine comparable anaesthetic depth. Sevoflurane or halothane were titrated to a SEF 90 of 8-12 Hz. Management of the airway was done with the RLMA (reinforced laryngeal mask). All patients were under controlled ventilation. At the end of surgery and anaesthesia 3 time intervals were measured: phase I) end of anaesthetic application--start of spontaneous respiration; phase II) start of spontaneous respiration--removal of RLMA. The SEF 90 interval was also assessed. RESULTS: 18 cases were included (halo n = 8/sevo n = 10, no significant differences concerning weight, age, anaesthesia time). There is a significant advantage for the Sevoflurane group in phase II of 6.8 minutes. No differences were seen in phase I and SEF 90 interval. CONCLUSION: Sevoflurane offers the potential for shortening turnover in pediatric anaesthesia.