[Optimization of blood gas analysis in intensive care units : Reduction of preanalytical errors and improvement of workflow]. / Optimierung von Blutgasanalysen auf der Intensivstation : Reduzierung präanalytischer Fehler und Verbesserung der zeitlichen Abläufe.

BACKGROUND: Point of care testing with blood gas analysis (BGA) is an important factor for intensive care medicine. Continuous efforts to optimize workflow, improve safety for the staff and avoid preanalytical mistakes are important and should reflect quality management standards. AIM: In a prospective observational study it was investigated whether the implementation of a new system for BGA using labeled syringes and automated processing of the specimens leads to improvements compared to the previously used procedure. MATERIAL AND METHODS: In a 4-week test period the time until receiving the final results of the BGA with the standard method used in the clinical routine (control group) was compared to the results in a second 4-week test period using the new labeled syringes and automated processing of the specimens (intervention group). In addition, preanalytical mistakes with both systems were checked during routine daily use. Finally, it was investigated whether a delay of 10 min between taking and analyzing the blood samples alters the results of the BGA. RESULTS: Preanalytical errors were frequently observed in the control group where non-deaerated samples were recorded in 87.3 % but in the intervention group almost all samples (98.9 %) were correctly deaerated. Insufficient homogenization due to omission of manual pivoting was seen in 83.2 % in the control group and in 89.9 % in the intervention group; however, in the intervention group the samples were homogenized automatically during the further analytical process. Although a survey among the staff revealed a high acceptance of the new system and a subjective improvement of workflow, a measurable gain in time after conversion to the new procedure could not be seen. The mean time needed for a complete analysis process until receiving the final results was 244 s in the intervention group and 201 s in the control group. A 10-min delay between taking and analyzing the blood samples led to a significant and clinically relevant elevation of the values for partial pressure of oxygen (pO2) in both groups compared to the results when analyzing the samples immediately (118.4 vs. 148.6 mmHg in the control group and 115.3 vs. 123.7 mmHg in the intervention group). When using standard syringes the partial pressure of carbon dioxide (pCO2) was significantly lower (40.5 vs. 38.3 mmHg) whereas no alterations were seen when using the labeled syringes. CONCLUSION: The implementation of a new BGA system with labeled syringes and automated processing of the specimens was possible without any difficulties under daily clinical routine conditions in this 10-bed intensive care unit (ICU). A gain of time could not be measured but a reduction in preanalytical errors using the labeled syringes with automated processing was found. Delayed analysis of blood samples can lead to significant changes in pO2 and pCO2 depending on the type of syringe used.

Analysis of the economic burden of diagnosis and treatment of tuberculosis patients in rural China.

SETTING: A county in Jiangsu Province, China. OBJECTIVES: To estimate the costs of the diagnosis and treatment of tuberculosis (TB) from the patient's perspective and to identify determinants of the patient's financial burden. DESIGN: In a cross-sectional survey, we interviewed 316 patients diagnosed from January 2010 to May 2011 who had already completed their anti-tuberculosis treatment. The financial burden on TB patients included out-of-pocket costs and productivity losses. RESULTS: The average per capita total out-of-pocket cost was 3024.0 Chinese yuan (CNY), with a median cost of 1086 CNY (interquartile range [IQR] 480-2456). Mean out-of-pocket medical and non-medical costs were respectively 2565.7 CNY and 458.3 CNY. Productivity lost by patients and family members was 2615.2 CNY (median 500, IQR 250-2025). Factors associated with out-of-pocket costs and productivity losses included hospitalisation, adverse drug reactions, cost of drugs to 'protect' the liver, cost of second-line anti-tuberculosis drugs and diagnostic delay. CONCLUSION: Although the government of China has implemented a 'free TB service policy', the economic burden on patients is still heavy. More patient-centred interventions are essential to reduce the financial burden on patients.

[Secondary sclerosing cholangitis after multiple trauma and long-term intensive care treatment: case report of a characteristic course]. / Sekundär-sklerosierende Cholangitis nach Polytrauma und Langzeitintensivtherapie : Fallbericht eines charakteristischen Verlaufs.

This article reports on a patient who needed intensive care treatment because of multiple trauma. The patient had no preexisting liver disease but developed secondary sclerosing cholangitis and finally died. The etiology, diagnosis and therapeutic options of this clinical picture are discussed and a review of the literature is presented.

Coma after spinal anaesthesia in a patient with an unknown intracerebral tumour.

Spinal anaesthesia is contraindicated in patients with elevated intracranial pressure or space-occupying intracranial lesions. Drainage of the lumbar cerebrospinal fluid (CSF) can increase the pressure gradient between the spinal, supratentorial and infratentorial compartments. This can result in rapid herniation of the brain stem or occluding hydrocephalus. We present a case of a female patient with an occult brain tumour who received a spinal anaesthesia for an orthopaedic procedure. The primary course of anaesthesia was uneventful. Several hours after surgery, the patient became increasingly disoriented and agitated. The next day, she was found comatose. A computed tomogram of the head revealed herniation of the brain stem, resulting in an occluding hydrocephalus due to a prior not known infratentorial mass. By acute relieving of the intracranial pressure by external CSF drainage, the mass was removed 2 days later. The further post-operative course was uneventful and the patient was discharged from the hospital without neurological deficit 3 weeks after the primary surgery.

Elevated premorbid body mass index is not associated with poor neurological outcome in the subacute state after aneurysmal subarachnoid hemorrhage.

BACKGROUND: An elevated body mass index (BMI) is suggested to be a risk factor for a poor outcome after intracranial aneurysm rupture and is considered to be associated with cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to analyze the association between permorbid BMI and neurological outcome. METHODS: In this retrospective study, the patients' BMI at the time of their admission to hospital was correlated to their neurological outcome as measured by the Glasgow outcome score after two weeks and two months of treatment. RESULTS: In contrast to other studies, there were no significant correlations between premorbid BMI and neurological outcome, shunt requirement, tracheotomy requirement and duration of stay on the intensive care unit (ICU). CONCLUSIONS: Overweight patients have no higher risk of a poor neurological outcome after aneurysmal SAH if premorbid risk factors such as hypertension and hyperglycemia are carefully modified throughout the period of critical care.

[Noise in intensive care units. Do the alarms for subspecialties differ]. / Lärm auf der Intensivstation: Unterscheiden sich die Alarme in den Fachdisziplinen?

INTRODUCTION: Cardiovascular monitoring alarms are frequent in intensive care units (ICUs) and lead to noise levels often exceeding 80 dB. The aim of this study was to evaluate if there are relevant differences between ICUs with different subspecialties in the frequency and distribution of alarm signals, their occurrence during the day, the types of alarms and the underlying vital parameters. METHODS: All alarm signals of the cardiovascular monitoring systems from randomly chosen patients at five different ICUs of the university hospital of Regensburg were evaluated. RESULTS: No significant differences between the ICUs regarding the frequency of alarm signals and only slight differences in the time distribution could be recognized (p=0.02). The most frequent alarm signals were from threshold alarms (61%) followed by technical alarms. The majority of alarms generated were related to invasive arterial blood pressure measurement. CONCLUSIONS: The frequency and distribution of ICU alarm signals seem to be comparable on different ICUs. Therefore, implementation of universal concepts for alarm reduction seems to be applicable regardless of the subspecialty of the ICU.

[The importance of dental-based treatment shown on the case report of a pontine abscess caused by Streptococcus viridans]. / Die Bedeutung der zahnbezogenen Focussanierung am Fallbeispiel eines pontinen Abszesses durch Streptokokken der Viridans Gruppe.

BACKGROUND: The treatment of infectious oral lesions is an important prophylactic procedure preceding immunsuppressive therapy. The case reported underlines the importance of this treatment by showing severe complications of an infective dental focus in an immunocompetent patient. CASE REPORT: A 65 year old patient was referred to hospital due to neurological disorders including hypaesthesia, movement deficits, nausea and falls. Because of progressive aggravation with hemiplegia a craniotomy and biopsy of a suspicious area in the pons was performed. A brain stem abscess caused by Streptococcus viridans was diagnosed. Brain stem abscesses are very rare events who contribute to only about 0.6%-6% of all intracranial abscesses. The intraoral inspection revealed a periodontally diseased and carious affected dentition with many missing teeth. Other foci were ruled out. Because of persistency of the symptoms another operation with abscess drainage was performed. Afterwards the clinical symptoms improved but hemiplegia was still present. CONCLUSIONS: Even minor dental procedures as well as existence of a carious or periodontal disease may cause bacteremia with severe septical implications. Patients at risk (e.g. dieases of the heart valves or diabetes) should always treated with an antibiotic prophylaxis before treatment according to the guidelines of the DGZMK. All oro-pharyngeal infectious foci have to be treated sufficiently to prevent sceptical complications. Even more important is the prophylactic treatment preceding chemo- or radiation therapy.

[Hb 1.1 g/dl: successful treatment of a polytraumatized patient in hemorrhagic shock]. / Hb=1,1 g/dl: erfolgreiche Behandlung nach Polytrauma mit schwerem hämorrhagischen Schock. Effektives Zusammenspiel von präklinischer Versorgung, Schockraummanagement und Intensivtherapie.

We report on the successful treatment of a seriously traumatized patient (injury severity score=59) who presented with exsanguinating hemorrhage in the emergency room. Preclinical and emergency room management included "small volume" hypertonic resuscitation as well as massive transfusion, C-clamp stabilization of a pelvic ring instability, and attachment of external fixators to multiple bone fractures. During the intensive care period,we started enteral immunonutrition immediately after an abdominal compartment syndrome was removed by laparotomy and a jejunal catheter had been inserted. Multiple fractures were stabilized rapidly and the soft tissue wounds were covered by split skin grafts. Additionally, we provided sufficient analgesia with few side effects using an epidural catheter for continuous application of local anesthetics. In summary, an effective synthesis of up-to-date strategies for preclinical, emergency room, and intensive care management prevented multiple organ failure and achieved survival with good quality of life after a "fatal" multiple trauma.

Lung recruitment maneuver in patients with cerebral injury: effects on intracranial pressure and cerebral metabolism.

OBJECTIVE: To investigate the effects of a lung recruitment maneuver on intracranial pressure (ICP) and cerebral metabolism in patients with acute cerebral injury and respiratory failure. DESIGN: Prospective investigation. SETTING: Ten-bed intensive care unit of a university hospital. PATIENTS: Eleven patients with acute traumatic or non-traumatic cerebral lesions, who were on mechanical ventilation with acute lung injury. INTERVENTIONS: Hemodynamics, ICP, cerebral perfusion pressure (CPP), jugular venous oxygen saturation (SJO(2)), and arterial minus jugular venous lactate content difference (AJDL) were measured before, during and after a volume recruitment maneuver (VRM), which included a 30-s progressive increase in peak pressure up to 60 cmH(2)O and a sustained pressure at the same level for the next 30 s. RESULTS: At the end of VRM, ICP was elevated (16+/-5 mmHg vs 13+/-5 mmHg before VRM, P<0.05) and mean arterial pressure was reduced (75+/-10 vs 86+/-9 mmHg, P<0.01), which resulted in a decrease of CPP (60+/-10 vs 72+/-8 mmHg, P<0.01). SJO(2) deteriorated at the end of the procedure (59+/-7 vs 69+/-6%, P<0.05), AJDL was not altered. In the following period all parameters returned to normal values. An improvement in arterial oxygenation was observed at the end, but not in the period after the maneuver. CONCLUSIONS: Our VRM reduced cerebral hemodynamics and metabolism. We conclude that our VRM with high peak pressure effects only a marginal improvement in oxygenation but causes deterioration of cerebral hemodynamics. We therefore cannot recommend this technique for the ventilatory management of brain-injured patients.

[Fatal intracerebral gas gangrene in a 10-month-old child]. / Tödlich verlaufende intrazerebrale Gasbrandinfektion bei einem zehn Monate alten Kind.

Today, intracerebral infections by gas forming bacteria are very rare. They are mostly seen after penetrating injuries and more rarely after trivial trauma. Although prognosis of this kind of infection is severe, the general outcome of these patients after surgical and antibiotic treatment is good. We report a ten months old boy suffering a pecking injury just above the left ear with perforation of the temporal bone and dura. In between 48 hrs he developed a rapidly progressive gas gangrene encephalitis due to infection with C. perfringens and died despite of surgical and antibiotic treatment due to massive brain swelling and cardio-pulmonary failure.

Ossifying lipoma.

Lipomas are very common, but osseous changes within these tumours are rare. A lipoma with osseous components is presented, with an overview of the literature and pathogenesis of this unusual lesion and considerations relating to the differential diagnosis.

Expression of cerebellar specific glutamate and GABAA receptor subunits in heterotopic cerebellar grafts.

In the cerebellum, up- and downregulation of specific GABAA and NMDA receptor subunits coincide with granule cell migration and differentiation. In this study, in situ hybridization techniques with GABAA and NMDA receptor subunit specific probes were employed to assess whether the molecular phenotype of heterotopically grafted cerebellar granule cells corresponds to that of normal cerebellum. The cerebellar anlage of rat fetuses was stereotactically grafted into the rostral striatum of adult rats. Eight weeks after transplantation, analysis demonstrated acquisition of an adult differentiation status reflected by abundant GABAA alpha 6 and NR2C mRNA expression in granule cells. Complete lack of NR2B transcripts, molecular markers of immature granule cells, argues against persistence of undifferentiated cells. The data suggest that intrinsic cell-autonomous factors largely determine the molecular commitment of granule cells and that a restricted specific environment is not necessary to promote granule cell differentiation.

Editing of GluR2 RNA in the gerbil hippocampus after global cerebral ischemia.

Postischemic delayed neuronal death (DND) in CA1 of the gerbil hippocampus is thought to be caused by an abnormal increase of Ca2+ influx into the cell, mediated by excessive activation of glutamate receptors. One subtype of glutamate receptors, the AMPA receptor, is not permeable to calcium ions as long as an edited form of its GluR2 subunit is present. It is possible that global ischemia interferes with the posttranscriptional editing of the GluR2 mRNA and thus leads to calcium influx via the AMPA receptor. In order to test this hypothesis, we examined the extent of GluR2 RNA editing in CA1 and CA3 microdissected from gerbil hippocampus after 5 min of global ischemia and various recirculation intervals. At each interval tested, quality and quantity of mRNA editing in the vulnerable CA1 region were the same as in CA3. Furthermore, postischemic mRNA editing in both hippocampal regions was indistinguishable from editing in untreated control animals. Our results clearly demonstrate that global ischemia does not cause impairment of GluR2 RNA editing, which is thus not responsible for the abnormal calcium permeability of the postischemic cell membrane.

Embryonic cortical neurons differentiate into various types of interneurons when heterotopically transplanted into the adult rat brain.

The adult cortex represents a heterogeneous mixture of different classes of pyramidal neurons and non-pyramidal interneurons. After grafting embryonic cortical anlage into the adult striatum, the present study investigated whether the development of different populations of interneurons in heterotopic cortical grafts is similar to the adult cortex. The presence of specific subpopulations of interneurons in grafts was assessed by immunocytochemistry using various antibodies against marker molecules for interneurons such as neuropeptides and calcium-binding proteins. These molecules are expressed to a different extent in specific subpopulations of cortical interneurons. Cortical primordia obtained on embryonic day 14 (E14) were stereotactically grafted into the center of the left striatum of adult recipient rats. After an 8-week differentiation period, host rats were perfusion fixed and immunocytochemistry was performed using antibodies against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin, parvalbumin and calbindin D-28k. Within the grafts, the number of immunopositive interneurons as well as the intensity of immunostaining for different marker molecules corresponded well with those of the adult cortex. In contrast, the expression pattern in the graft demonstrated clear differences when compared with the surrounding host striatum. The present study demonstrates, that at E14 at least some cells of the cortical anlage are primed to develop into different classes of interneurons independent of their normal environment and their regular synaptic connections. Thus, different interneuron progenitor cells survive transplantation and develop cell-specific morphological and cytochemical characteristics. Differentiation into various subpopulations of neurons may be a prerequisite for potential therapeutic approaches in humans.

c-JUN, KROX-24, and c-FOS expression in hippocampal grafts placed in excitotoxic hippocampal lesions of the rat.

Hippocampal transplants were examined for the expression of three specific immediate early gene encoded proteins in order to establish if grafted immature tissue maintains the basic molecular program necessary for gene transcription after grafting to excitotoxic (ibotenic acid-induced) lesions in adult host rat brains. The transplants were derived from newborn donor rats and were analyzed immunocytochemically for the presence of c-JUN, KROX-24, and c-FOS transcription factors 5 months after grafting. The expression and distribution patterns of these genes in the host hippocampus were identical to those in hippocampal neurons of normal untreated animals. c-JUN-, KROX-24-, and c-FOS-labeled neurons were also present in the transplants, where KROX-24 and c-FOS exhibited a distribution similar to host hippocampus. In contrast, c-JUN was more extensively expressed in the transplants, suggesting a molecular response to the grafting conditions and the actual graft-host brain interactions.

Developmental expression of GAP-43 and SNAP-25 in heterotopic rat cortical grafts.

In situ hybridization techniques were used to assess (i) whether the temporal developmental profiles of the nervous system specific growth associated phosphoprotein (GAP-43) and the 25-kDa synaptosomal-associated protein (SNAP-25) are maintained in heterotopic cortical transplants, and (ii) whether the hybridization intensity in morphologically differentiated heterotopic transplants is comparable to that in the cortex of host animals. Cortical primordia at embryonic day 14 were stereotactically grafted into the striatum of adult recipient rats. Grafts at days 4, 7, 14, 35 and 56 after transplantation demonstrated developmental changes with a progressive decline of GAP-43 and a continuous up-regulation of SNAP-25 expression. Our data provide evidence of distinct molecular alterations during the differentiation process of cortical grafts, which are strikingly similar to previous studies investigating the temporal profile and intensity of GAP-43 and SNAP-25 gene expression in normal developing cortex of the rat.

Functional N-methyl-D-aspartate receptors develop and persist in heterotopic cortical grafts and regulate expression of transcription factor KROX-24.

N-Methyl-D-aspartate (NMDA) receptors are a major subfamily of glutamate receptors and thought to play a pivotal role in developmental plasticity and synaptogenesis, neuronal migration and differentiation. NMDA receptors have also been implicated in neuronal degeneration, as glutamate binding to the receptor initiates rapid excitotoxic signal transduction. Molecular cloning of cDNAs has yielded different NMDA receptor subtypes with an essential NR1 subunit associated with various modulatory NR2 subunits. The NR1 gene is expressed at high levels in virtually all brain structures, but to a distinctly higher extent in cortex than in striatum. Here we report on the development, maintenance and function of glutamate receptors in intrastriatally located cortical grafts. Cortical primordia of rat fetuses (El4) were stereotactically grafted into the rostral striatum of adult recipient rats. Expression of NR1 mRNA was examined by in situ hybridization after post transplantation periods of 2, 6 and 12 months. Analysis of NR1 mRNA expression in grafts after a differentiation period of 2 months revealed equal levels compared to the intact neocortex of the host rats and that of rats with the same ontogenetic age. No downregulation of NR1 mRNA was seen 6 and 12 months after transplantation. To ensure normal function of NMDA receptors in grafts, we studied the effects of a blockade of receptor dependent gene expression, using Krox-24 as a reporter gene. In normal brain tissue, constitutive expression of KROX-24 protein is thought to be maintained by NMDA receptor mediated physiological synaptic activity and can be abolished by the non-competitive NMDA receptor antagonist MK-801. Immunostaining of KROX-24 protein was almost identical in grafts compared to the corresponding neocortex. This constitutive expression of KROX-24 could be abolished by treatment with MK-801. Thus, our data indicate normal development and long term persistence of glutamate receptors with intrinsic excitatory activity in transplants.

Concurrent immediate early gene induction by epileptic seizures in heterotopic cortical grafts and neocortex.

Cortical primordia of rat fetuses (gestation day 14) were stereotactically grafted into the rostral striatum of adult recipient rats. After 8 weeks, the transplants had developed into a highly differentiated population of mature neuroectodermal cells. Host rats were then subjected to 15 min of bicuculline-induced epileptic seizures or served as controls. Seizure-elicited immediate early gene (IEG) expression was investigated after various postictal survival times (up to 24 h), using immunocytochemistry with specific antisera against seven IEG encoded proteins (c-FOS, FOS B, c-JUN, JUN B, JUN D, KROX-24, KROX-20). Constitutive IEG expression in intra striatum grafted neocortical neurons was identical to that in the corresponding host neocortex. In particular, abundant KROX-24 and lack of c-JUN expression implies the establishment of synaptic contacts within the graft or with the host circuitry. Postictal expression kinetics of individual IEG encoded proteins within the transplants were strikingly similar to those seen in the neocortex in situ. c-FOS and KROX-24 were most rapidly induced, followed by c-JUN and JUN B, and a more delayed induction of FOS B, JUN D and KROX-20. Apart from a slightly prolonged c-FOS expression in grafts, individual transcription factors remained elevated for different time periods and showed a concurrent decline in transplants and in neocortex in situ. In conclusion, IEG induction in grafts closely paralleled that in the host neocortex but differed from the adjacent striatum which exhibited no c-JUN induction at any time point investigated. These results indicate that following an appropriate differentiation period, heterotopically grafted embryonic cortical neurons respond to extracellular stimuli with changes of gene expression that closely resemble the normal host cortex. This suggests development of a similar molecular phenotype, including proper acquisition and intracellular processing of information.

The KROX-20 transcription factor in the rat central and peripheral nervous systems: novel expression pattern of an immediate early gene-encoded protein.

The KROX-20 protein (also termed EGR-2) is encoded by an immediate early gene cloned by cross-hybridization to the Drosophila melanogaster Krüppel gene. It belongs to a class of transcription factors with zinc finger motifs and binding activity to a transcriptional regulatory DNA element termed the early growth response consensus sequence. In the present study the temporospatial expression of KROX-20 was investigated in the central and peripheral nervous systems of normal rats and after various stimuli known to induce immediate early genes, including epileptic seizures, axotomy, pharmacological treatment with glutamate and alpha-adrenergic receptor antagonists, and peripheral noxious stimulation. Immunocytochemistry was performed with a specific polyclonal antiserum generated against a fusion protein containing KROX-20 sequences. In the central nervous system, KROX-20 protein demonstrated distinct constitutive nuclear expression in specific neuronal subpopulations of the cortex, septum, amygdala, olfactory bulb and hypothalamus. In addition, distinct cytoplasmic immunoreactivity was present in spinal and medullary motoneurons, dorsal root ganglion neurons and a few neuronal cell populations of midbrain and forebrain. In the CNS, KROX-20 was only induced by bicuculline-induced epileptic seizures. Topographically, the postictal increase of KROX-20 levels was restricted to areas with constitutive expression, such as cerebral cortex, fornix and amygdala. Induction of KROX-20 peaked at 4-8 h after onset of seizure activity. No increase in immunoreactivity was observed in the hippocampus, the brain region most severely affected by bicuculline-induced seizures. Transection of central and peripheral nerve fibers did not result in KROX-20 induction in axotomized neurons. However, KROX-20 was induced in Schwann-like cells after transection of the sciatic nerve. In contrast to KROX-20, KROX-24, a related transcription factor of the zinc finger family, was markedly induced in hippocampal and spinal neurons following seizures and peripheral noxious stimulation, respectively, as well as in CNS neurons following axotomy. Our data indicate that KROX-20 represents an immediately early gene product with basal expression in selected neuronal populations of the nervous system and a restricted inducibility after intentional stimuli.