Heimo Wissing

Improved detection of blood stream pathogens by real-time PCR in severe sepsis.

ObjectiveEvaluation of the technical and diagnostic feasibility of commercial multiplex real-time polymerase chain reaction (PCR) for detection of blood stream infections in a cohort of intensive care unit (ICU) patients with severe sepsis, performed in addition to conventional blood cultures.DesignDual-center cohort study.SettingSurgical ICU of two university hospitals.Patients and participantsOne hundred eight critically ill patients fulfilling the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) severe sepsis criteria were included.InterventionsNone.Measurements and resultsPCR results obtained in 453 blood samples from 108 patients were compared with corresponding blood culture results. PCR resulted in a twofold higher positivity rate when compared with conventional blood culture (BC) testing (114 versus 58 positive samples). In 40 out of 58 PCR positive assays the results of the corresponding blood cultures were identical to microorganisms detected by PCR. In 18 samples PCR and BC yielded discrepant results. Compared with conventional blood culture the sensitivity and specificity of PCR was 0.69 and 0.81, respectively. Further evaluation of PCR results against a constructed gold standard including conventional microbiological test results from other significant patient specimen (such as bronchio-alveolar lavage fluid, urine, swabs) and additionally generated clinical and laboratory information yielded sensitivity of 0.83 and specificity of 0.93.ConclusionsOur cohort study demonstrates improved pathogen detection using PCR findings in addition to conventional blood culture testing. PCR testing provides increased sensitivity of blood stream infection. Studies addressing utility including therapeutic decision-making, outcome, and cost-benefit following diagnostic application of PCR tests are needed to further assess its value in the clinical setting.

Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis

Objectives: To evaluate the potential improvement of antimicrobial treatment by utilizing a new multiplex polymerase chain reaction (PCR) assay that identifies sepsis-relevant microorganisms in blood. Design: Prospective, observational international multicentered trial. Setting: University hospitals in Germany (n = 2), Spain (n = 1), and the United States (n = 1), and one Italian tertiary general hospital. Patients: 436 sepsis patients with 467 episodes of antimicrobial treatment. Methods: Whole blood for PCR and blood culture (BC) analysis was sampled independently for each episode. The potential impact of reporting microorganisms by PCR on adequacy and timeliness of antimicrobial therapy was analyzed. The number of gainable days on early adequate antimicrobial treatment attributable to PCR findings was assessed. Measurements and Main Results: Sepsis criteria, days on antimicrobial therapy, antimicrobial substances administered, and microorganisms identified by PCR and BC susceptibility tests. Results: BC diagnosed 117 clinically relevant microorganisms; PCR identified 154. Ninety-nine episodes were BC positive (BC+); 131 episodes were PCR positive (PCR+). Overall, 127.8 days of clinically inadequate empirical antibiotic treatment in the 99 BC+ episodes were observed. Utilization of PCR-aided diagnostics calculates to a potential reduction of 106.5 clinically inadequate treatment days. The ratio of gainable early adequate treatment days to number of PCR tests done is 22.8 days/100 tests overall (confidence interval 15–31) and 36.4 days/100 tests in the intensive care and surgical ward populations (confidence interval 22–51). Conclusions: Rapid PCR identification of microorganisms may contribute to a reduction of early inadequate antibiotic treatment in sepsis.

A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position

OBJECTIVEWe report the results and complications associated with standardized intraoperative management designed for the prevention of hemodynamically relevant venous air embolism during surgery performed in the semisitting position. METHODSA protocol for preoperative evaluation and intraoperative monitoring was developed and applied in 187 consecutive patients who underwent surgery in the semisitting position between 1999 and 2004. The protocol included preoperative transesophageal echocardiography examination (TEE), intraoperative TEE monitoring, catheterization of the right atrium and a combination of fluid input, positive end expiratory pressure, and standardized positioning aiming at a positive pressure in the transverse and sigmoid sinuses. Data were collected retrospectively from the charts and intraoperative anesthesiological protocols of the patients for the incidence of clinically relevant air embolism (i.e., TEE-diagnosed air embolism plus a decrease in end tidal CO2 or hemodynamic changes) and other complications related to the semisitting position. RESULTSThree cases (1.6%) of relevant venous air embolism occurred in 187 patients. Only 1 case (0.5%) was hemodynamically relevant, with temporary arterial blood pressure decrease and heart rate increase. Pneumatocephalus leading to lethargy was a frequent postoperative finding, which resolved spontaneously in all except 1 patient with epileptic seizure and oculomotor nerve palsy attributable to space-occupying subdurally trapped air, which had to be treated surgically. There was no permanent morbidity or mortality related to the semisitting position. CONCLUSIONFear of massive venous air embolism is one reason for dramatic decline in the use of the semisitting position in neurosurgical practice. We found that strict adherence to a standardized protocol using TEE monitoring before and during surgery; exclusion of patients with patent foramen ovale; and a combination of positive end expiratory pressure, fluid input, and a standardized position aiming a positive pressure in the transverse and sigmoid sinuses helped to greatly minimize this complication to a rate of 0.5% for hemodynamically relevant events.

Carbon Monoxide Production from Desflurane, Enflurane, Halothane, Isoflurane, and Sevoflurane with Dry Soda Lime

Background Previous studies in which volatile anesthetics were exposed to small amounts of dry soda lime, generally controlled at or close to ambient temperatures, have demonstrated a large carbon monoxide (CO) production from desflurane and enflurane, less from isoflurane, and none from halothane and sevoflurane. However, there is a report of increased CO hemoglobin in children who had been induced with sevoflurane that had passed through dry soda lime. Because this clinical report appears to be inconsistent with existing laboratory work, the authors investigated CO production from volatile anesthetics more realistically simulating conditions in clinical absorbers. Methods Each agent, 2.5 or 5% in 2 l/min oxygen, were passed for 2 h through a Dräger absorber canister (bottom to top) filled with dried soda lime (Drägersorb 800). CO concentrations were continuously measured at the absorber outlet. CO production was calculated. Experiments were performed in ambient air (19–20°C). The absorbent temperature was not controlled. Results Carbon monoxide production peaked initially and was highest with desflurane (507 ± 70, 656 ± 59 ml CO), followed by enflurane (460 ± 41, 475 ± 99 ml CO), isoflurane (176 ± 2.8, 227 ± 21 ml CO), sevoflurane (34 ± 1, 104 ± 4 ml CO), and halothane (22 ± 3, 20 ± 1 ml CO) (mean ± SD at 2.5 and 5%, respectively). Conclusions The absorbent temperature increased with all anesthetics but was highest for sevoflurane. The reported magnitude of CO formation from desflurane, enflurane, and isoflurane was confirmed. In contrast, a smaller but significant CO formation from sevoflurane was found, which may account for the CO hemoglobin concentrations reported in infants. With all agents, CO formation appears to be self-limited.

Interleukin-22 detected in patients with abdominal sepsis.

Interleukin 22 (IL-22) is a TH17-like cytokine known to specifically activate epithelial cells, thereby strengthening immune defense at host/environment interfaces. Animal studies suggest that IL-22 may play a crucial role in clinical sepsis. However, little is known about IL-22 in sepsis patients. In a single-center university hospital setting, serum IL-22 levels were assessed in 16 patients with the diagnosis of abdominal sepsis, 16 patients who have undergone elective major abdominal surgery without the diagnosis of sepsis, and 21 healthy volunteers. In accordance with current knowledge, we observed enhanced levels of IL-6 and IL-10 in serum specimens of sepsis patients compared with surgical control patients. Here, we report, for the first time, a modest but significant elevation of serum IL-22 detectable in abdominal sepsis patients (P < 0.001). Median serum concentrations of IL-22 were 111.8 pg/mL, 3.4 or 2.0 pg/mL, and 9.3 pg/mL for abdominal sepsis patients, surgical control patients (presurgery or postsurgery), and healthy volunteers, respectively. Interleukin 22 produced in the course of abdominal sepsis may contribute to host defense and stabilization of mucosal barrier functions under conditions of systemic infection.

Incidence of nausea and vomiting in children after strabismus surgery following desflurane anaesthesia

In a prospective, randomized parallel study, 60 ASA I–III children aged 1–17 years, scheduled for elective strabismus surgery, were anaesthetized with desflurane without prophylactic antiemetic medication. The objective of the study was to determine the incidence of postoperative nausea and vomiting after general anaesthesia with desflurane. To decide whether nitrous oxide further influences these symptoms, the patients were randomly assigned to two groups of 30 patients each. One group received desflurane in oxygen/air and a second group received desflurane in oxygen/nitrous oxide. In all children, after intravenous induction and tracheal intubation, anaesthesia was administered as minimal flow anaesthesia with oxygen and nitrous oxide or air according to the random plan. The patients were observed for 48 postoperative hours until their discharge from the ward. The overall incidence of nausea was found to be 37%, and vomiting was seen in 32% of all patients. No statistical correlation was found between the incidence of postoperative emesis and the administration of nitrous oxide or the duration of general anaesthesia. Instead, the incidence of vomiting was 2.5‐fold higher when surgery was performed on both eyes compared with one eye. The relatively low incidence of postoperative nausea and vomiting, as well as the quick recovery from anaesthesia, permitting an early discharge from the postoperative care unit to the ward, show desflurane to be a suitable volatile anaesthetic in strabismus surgery in children.

Zur Temperaturentwicklung von Inhalationsanästhetika auf trockenem Atemkalk

ZusammenfassungAufgrund einiger Fallberichte, bei denen eine starke Erhitzung des Absorberbehälters bei Kontakt von Sevofluran und Enfluran mit ausgetrocknetem Atemkalk beobachtet wurde, untersuchten wir die Temperaturentwicklung im Atemkalkbehälter des DRÄGER ISO 8 Kreisteils bei Passage volatiler Anästhetika durch getrockneten Atemkalk. Methoden: Im Zentrum des Absorberbehälters bei 3 und 7,5 cm Höhe wurde die Temperatur kontinuierlich gemessen. Durch den mit ausgetrocknetem DRÄGERSORB 800 Atemkalk gefüllten Absorber wurden Desfluran, Enfluran, Isofluran und Sevofluran mit 5 Vol% in 2 l/min O2 sowie Halothan mit 4 Vol% in 2,5 l/min O2 geleitet. Am Inspirationsventil wurden die Atemgaskonzentrationen gemessen (DATEX Capnomac). Ergebnisse: Bei allen Inhalationsanästhetika wurde eine deutliche Wärmeentwicklung beobachtet mit Maximalwerten von 56–58 °C für Desfluran, 76–80 °C für Enfluran und Isofluran, 84–88 °C für Halothan und 126–130 °C für Sevofluran. Einige Inhalationsanästhetika wurden erst spät detektiert, teils war der Kurvenverlauf nicht plausibel, so daß andere IR-absorbierende Substanzen vermutet werden. Diskussion: Die hohen Temperaturen deuten auf Zersetzungsreaktionen hin. Für Desfluran, Enfluran, Halothan und Isofluran ist CO als ein Zersetzungsprodukt beim Kontakt mit trockenem Atemkalk bekannt. Mit feuchtem Atemkalk sind für Sevofluran die Compounds A–E als Zersetzungsprodukte beschrieben, für die Reaktion mit trockenem Atemkalk, bei der die höchsten Temperaturen gemessen wurden, liegen bislang keine Daten über neu entstehende Reaktionsprodukte vor.AbstractThere are some case reports about excessive heat production in the absorbent canister when sevoflurane or enflurane are washed into a circle containing dried soda lime. This observation was often made in the DRÄGER ISO 8 circle system with the gas inlet upstream of the soda lime canister with the gas-flow from bottom to top. Methods: The temperature in the center of an absorbent canister was measured 3.0 cm and 7.5 cm above the bottom. Soda lime (DRÄGERSORB 800) was dried in an O2 stream for 2–3 days until there was no further loss in weight. 5 Vol% of desflurane, enflurane, isoflurane and sevoflurane in 2 l/min O2 or 4 Vol% of halothane in 2.5 l/min O2 were continuously fed into the canister. The concentration of the respective inhalational agents were measured after the soda lime canister using a DATEX Capnomac. Experiments were performed at ambient temperatures of 20–22 °C. Results: A considerable temperature increase was achieved with all anaesthetics. The highest temperatures were measured at the upper sensor with 56–58 °C for desflurane, 76–80 °C for enflurane and isoflurane, 84–88 °C for halothane and 126–130 °C for sevoflurane. IR-detection for some agents was considerably delayed or the time course indicated that other compounds might have formed which absorb at the wavelength monitored. Discussion: The high temperatures indicate the degradation rather than absorption of the volatile anaesthetics. CO is known to be degradation product of all currently used volatile anaesthetics except sevoflurane. Sevoflurane, however, produced the highest temperatures passing through dried soda lime. There are no reports about new specific breakdown products for sevoflurane on dried soda lime.

Anisocoria during isoflurane anaesthesia in a six-year-old girl

A case report of transient anisocoria during routine anaesthesia in a six‐year‐old female, where isoflurane was suspected of causing unilateral mydriasis.

[Molecular biological detection of pathogens in patients with sepsis. Potentials, limitations and perspectives].

The wide variability of clinical symptoms and the ongoing difficulties concerning the rapid and specific laboratory diagnosis of sepsis, contribute to the fact that sepsis primarily remains a clinical diagnosis. To contribute to a more tailored antibiotic coverage of the patient early on in the course of the disease, modern diagnostic concepts favour the qualitative and quantitative molecular biological detection of blood stream pathogens directly from whole blood. This offers a very attractive alternative to the currently applied less sensitive and much more time-consuming blood culture-based laboratory methods. Moreover, recent study results suggest an increasing impact of molecular detection methods with short turn-around times for more effective treatment and better outcomes of patients with sepsis and septic shock. In the short term, such tests will not substitute conventional blood culture despite their superior rapidity and sensitivity, mainly because of higher cost. The amazing speed of ongoing scientific developments means, however, that techniques that might appear complicated, labour intensive, and costly today, will develop to become the future standards in the microbiological diagnosis of patients with sepsis and septic shock.ZusammenfassungDas klinisch variable Erscheinungsbild und die fortbestehenden Schwierigkeiten beim zeitnahen sensitiven und spezifischen laboratoriumsmedizinischen Infektionsnachweis machen die Sepsis immer noch zu einer schwierigen und zumeist primär klinischen Diagnose. Zeitgemäße Diagnostikkonzepte für eine direkte Erregerdiagnose aus Vollblut auf der Basis qualitativer und quantitativer molekularbiologischer Detektionsmethoden werden daher vielfach als ein interessanter Ausweg angesehen, um dem Dilemma einer wenig sensitiven und zumeist relativ zeitintensiven mikrobiellen Erregerdiagnostik auf der Basis klassischer Kulturverfahren zu entgehen und der Notwendigkeit Rechnung zu tragen, bei septischen Patienten möglichst frühzeitig eine erregerorientierte zielgerichtete Antibiotikatherapie zu initiieren. Zudem legen erste klinische Studienergebnisse die mögliche zukünftige Bedeutung sensitiver kulturunabhängiger Verfahren mit kurzen „Turn-around“-Zeiten für effektivere Therapiemöglichkeiten und ein besseres Outcome von Patienten mit schweren Infektionen wie Sepsis und septischem Schock nahe. Zunächst sind molekularbiologische Nachweise allerdings trotz vieler Vorteile bei Geschwindigkeit und Sensitivität als komplementäre Verfahren zu sehen und werden klassische Testverfahren wie die Blutkultur auch unter finanziellen Gesichtspunkten in vielen Bereichen nicht kurzfristig ersetzen können. Es ist aber damit zu rechnen, dass analog zur rasanten Entwicklung in anderen Technologiefeldern, molekularbiologische Verfahren, die heute noch als kompliziert, arbeitsaufwendig und teuer gelten, in Zukunft den Standard der infektiologischen und mikrobiologischen Diagnostik prägen werden.AbstractThe wide variability of clinical symptoms and the ongoing difficulties concerning the rapid and specific laboratory diagnosis of sepsis, contribute to the fact that sepsis primarily remains a clinical diagnosis. To contribute to a more tailored antibiotic coverage of the patient early on in the course of the disease, modern diagnostic concepts favour the qualitative and quantitative molecular biological detection of blood stream pathogens directly from whole blood. This offers a very attractive alternative to the currently applied less sensitive and much more time-consuming blood culture-based laboratory methods. Moreover, recent study results suggest an increasing impact of molecular detection methods with short turn-around times for more effective treatment and better outcomes of patients with sepsis and septic shock. In the short term, such tests will not substitute conventional blood culture despite their superior rapidity and sensitivity, mainly because of higher cost. The amazing speed of ongoing scientific developments means, however, that techniques that might appear complicated, labour intensive, and costly today, will develop to become the future standards in the microbiological diagnosis of patients with sepsis and septic shock.

Das Wärme-Feuchte-Profil des PhysioFlex

ZusammenfassungZiel: Das Wärme-Feuchte-Profil des Narkosegeräts PhysioFlex wurde am Modell beim Betrieb im geschlossenen System bestimmt. Methodik: An vier Meßstellen (Atemkalk, Geräteausgang, Geräteeingang, inspiratorisch vor dem Y-Stück) wurden der Temperatur- und Feuchteverlauf bei standardisierten Umgebungsbedingungen innerhalb der ersten 2 h nach Inbetriebnahme ermittelt. Ergebnisse: Nach 10 min herrschte an allen Meßorten Wasserdampfsättigung. Durch das konstruktionsbedingte Umwälzen des Systemvolumens mit 70 l/min kommt es zu einem schnellen Temperatur- und Feuchteausgleich im System. Die höchsten Werte (bis 32° C, bis 35 mg H2O/l Atemgas) werden über dem Atemkalk gemessen. Inspiratorisch werden im Mittel bereits nach 10 min mit 20 mg/l Feuchtewerte erreicht, die die minimalen Anforderungen an eine Narkosegasklimatisierung erfüllen. Nach 2 h werden mit annähernd 30 mg/l Feuchtewerte erreicht, die bislang an konventionellen Narkosegeräten nicht beschrieben werden konnten. Diskussion: Die im Vergleich zu konventionellen Narkosegeräten niedrigen Temperaturen über dem Atemkalk könnten den Einsatz thermolabiler Inhalationsanästhetika im PhysioFlex eher erlauben als in herkömmlichen Narkosegeräten unter „Minimal Flow”-Bedingungen. Der hohe Temperatur- und Feuchtegradient zwischen Atemkalk und Geräteausgang deutet auf einen Ansatzpunkt für eine weitere Optimierung hin.AbstractClosed-system anaesthesia provides the best prerequisites for optimal warming and humidification of anaesthetic gases. The PhysioFlex anaesthesia machine fascilitates quantitative closed-system anaesthesia. Furthermore, its design may improve the climatisation of the anaesthetic gases by revolving the system volume at 70 l/min, using a small soda-lime canister to allow optimal usage of the heat and moisture generated by CO2 absorption and by integrating all system components in thermally isolating housing. To determine the capacity of the PhysioFlex to climatise anaesthetic gases, we evaluated the heat and humidity profile at four characteristic places in the anaesthetic circuit under standardised conditions in a model. Materials and methods: In an air-conditioned room at 19–20° C ambient temperature, the PhysioFlex was operated with a fresh gas flow of less than 500 ml/min, similar to quantitative closed-system anaesthesia in adults. With a respiratory rate of 10/min and a tidal volume of 600 ml, a humidifier was ventilated, that delivered humidity-saturated gas at 33–34° C; 200 ml/min CO2 were added to the system at the humidifier to mimic the heat, moisture, and CO2 input of a patient into the anaesthetic circuit. A total of six series were performed, each starting with a cold and dry anaesthetic circuit. For 2 h the time-courses of temperature and humidity of the anaesthetic gases were measured at four distinct places: (1) in the soda-lime canister (M1); (2) at the outlet of the anaesthesia machine (M2); (3) at the inlet of the anaesthesia machine (M3); and (4) in the inspiratory limb close to the Y-piece (M4). Capacitive humidity sensors (VAISALA Type HMM 30 D without a protective cap) and very small thermocouples were used to measure relative humidity (rH) and temperature. The data were recorded at 5 min intervals. Due to the continuous gas stream in the system, the response time of the sensors, which is in the range of a few seconds, did not affect the accuracy of the measurement. With the temperature-dependent humidity content of 100% rH obtained from equation 1, absolute humidity was calculated. Results: The time courses of temperature and humidity at the different measuring points are depicted in Figs. 2 and 3, respectively. The steepest increase in temperature and humidity was observed at M1. Within 10 min 100% rH was achieved at all measuring points. Initially, there was a considerable temperature gradient between M1 and M2; this became gradually smaller, indicating system components with high heat capacities. There was only a small gradient between M2 and M4, indicating that there was only a small heat loss compared to the heat input. The recommended minimal climatisation of the anaesthetic gases of 20 mg H2O/l [20] was obtained within 10 min at M4. During the whole measuring period heat and humidity increased in the system, reaching a maximum at M4 after 120 min with average values of more than 28° C and 27 mg H2O/l, respectively. Conclusion: With the PhysioFlex anaesthesia machine employing closed-system conditions, minimal climatisation of anaesthetic gases was reached within 10 min. After a period of 120 min, the anaesthetic gases were nearly climatized to the extent recommended for long-term respirator therapy. To date, no comparable temperature and humidity level has been reported with conventional anaesthesia machines. The time course of the gradient between M1 and M2 may give an opportunity for further optimising the system in reducing heat loss after the soda-lime canister, the active heat and moisture source in the circuit. At about 32° C, the temperature in the soda-lime canister is 10–15° C less than in conventional anaesthesia machines. Thus, the use of thermally instable volatile anaesthetics in the PhysioFlex under closed-system conditions may be less critical than in conventional anaesthesia machines under minimal-flow conditions.