Harald Fritz

Role of fiberoptic bronchoscopy in conjunction with the use of double-lumen tubes for thoracic anesthesia: a prospective study.

Background Fiberoptic bronchoscopy has been recommended to verify the position of double‐lumen tubes (DLT), but this remains controversial. The authors studied the role of bronchoscopy for placing and monitoring right‐ and left‐sided DLTs after blind intubation and after positioning the patient. Methods Two hundred patients having thoracic surgery requiring DLT insertion were prospectively studied. “Blind” tracheal intubations were done with 163 left‐sided and 37 right‐sided disposable polyvinyl chloride Robertshaw tubes. Bronchoscopy was performed by a different anesthesiologist after intubation and conventional clinical verification of correct placement and after patient positioning for thoracotomy. A DLT was considered malpositioned when it had to be moved > 0.5 cm to correct its position. Critical malpositions were those that might have affected patient safety or influenced the surgical procedure if left uncorrected. Results After “blind” DLT intubation, clinical evidence of malpositioning was found in 28 patients. This was confirmed by fiberoptic assessment. In 172 patients in whom placement was judged correct by clinical assessment, malpositioning was detected by bronchoscopy in 79 cases, 25 of which were critical. After patient positioning, DLTs were found to be displaced in 93 patients, 48 of which were critical. Right‐sided DLTs were significantly more likely to be malpositioned than were left‐sided DLTs. Two complications were related to unsatisfactory lung separation in the 200 patients studied. Conclusions After blind intubation and patient positioning, more than one third of DLTs required repositioning. Routine bronchoscopy is therefore recommended after intubation and after patient positioning.

Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis: A Randomized Trial

CONTEXT Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains controversial. OBJECTIVE To compare the effect of moxifloxacin and meropenem with the effect of meropenem alone on sepsis-related organ dysfunction. DESIGN, SETTING, AND PATIENTS A randomized, open-label, parallel-group trial of 600 patients who fulfilled criteria for severe sepsis or septic shock (n = 298 for monotherapy and n = 302 for combination therapy). The trial was performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. INTERVENTIONS Intravenous meropenem (1 g every 8 hours) and moxifloxacin (400 mg every 24 hours) or meropenem alone. The intervention was recommended for 7 days and up to a maximum of 14 days after randomization or until discharge from the intensive care unit or death, whichever occurred first. MAIN OUTCOME MEASURE Degree of organ failure (mean of daily total Sequential Organ Failure Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse organ failure); secondary outcome: 28-day and 90-day all-cause mortality. Survivors were followed up for 90 days. RESULTS Among 551 evaluable patients, there was no statistically significant difference in mean SOFA score between the meropenem and moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 95% CI, 7.5-8.4 points) (P = .36). The rates for 28-day and 90-day mortality also were not statistically significantly different. By day 28, there were 66 deaths (23.9%; 95% CI, 19.0%-29.4%) in the combination therapy group compared with 59 deaths (21.9%; 95% CI, 17.1%-27.4%) in the monotherapy group (P = .58). By day 90, there were 96 deaths (35.3%; 95% CI, 29.6%-41.3%) in the combination therapy group compared with 84 deaths (32.1%; 95% CI, 26.5%-38.1%) in the monotherapy group (P = .43). CONCLUSION Among adult patients with severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone did not result in less organ failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00534287.

The Effect of Mild Hypothermia on Plasma Fentanyl Concentration and Biotransformation in Juvenile Pigs

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 ± 1.1 kg) were anesthetized by IV fentanyl (15 &mgr;g · kg−1 · h−1) and midazolam (1.0 mg · kg−1 · h−1). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6° ± 0.2°C for 6 h and were then rewarmed and kept normothermic at 37.7° ± 0.3°C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% ± 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% ± 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.

A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.

Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, Sao2 and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). Implications Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.

Coupling of Cerebral Blood Flow and Oxygen Metabolism in Infant Pigs During Selective Brain Hypothermia

Studies documenting the cerebral hemodynamic consequences of selective brain hypothermia (SBH) have yielded conflicting data. Therefore, the authors have studied the effect of SBH on the relation of cerebral blood flow (CBF) and CMRO2 in the forebrain of pigs. Selective brain hypothermia was induced in seven juvenile pigs by bicarotid perfusion of the head with extracorporally cooled blood. Cooling and stepwise rewarming of the brain to a Tbrain of 38°C, 25°C, 30°C, and 38°C at normothermic Ttrunk (38°C) decreased CBF from 71 ± 12 mL 100 g−1 min−1 at normothermia to 26 ± 3 mL 100 g−1 min−1 and 40 ± 12 mL 100 g−1 min−1 at a Tbrain of 25°C and 30°C, respectively. The decrease of CMRO2 during cooling of the brain to a Tbrain of 25°C resulted in a mean Q10 of 2.8. The ratio between CBF and CMRO2 was increased at a Tbrain of 25°C indicating a change in coupling of flow and metabolism. Despite this change, regional perfusion remained coupled to regional temperatures during deep cerebral hypothermia. The data demonstrate that SBH decreases CBF and oxygen metabolism to a degree comparable with the cerebrovascular and metabolic effects of systemic hypothermia. The authors conclude that, irrespective of a change in coupling of blood flow and metabolism during deep cerebral hypothermia, cerebral metabolism is a main determinant of CBF during SBH.

Secondary injuries in brain trauma: effects of hypothermia.

Hypothermia has been shown to be cerebroprotective in traumatized brains. Although a large number of traumatic brain injury (TBI) studies in animals have shown that hypothermia is effective in suppressing a variety of damaging mechanisms, clinical investigations have shown less consistent results. The complexity of damaging mechanisms in human TBI may contribute to these discrepancies. In particular, secondary injuries such as hypotension and hypoxemia may promote poor outcome. However, few experimental TBI studies have employed complex models that included such secondary injuries to clarify the efficacy of hypothermia. This review discusses the effects of hypothermia in various TBI models addressing primary and acute secondary injuries. Included are recently published clinical data using hypothermia as a therapeutic tool for preventing or reducing the detrimental posttraumatic secondary injuries and neurobehavioral deficits. Also discussed are recent successful applications of hypothermia from outside the TBI realm. Based on all available data, some general considerations for the application of hypothermia in TBI patients are given.

Effect of mild hypothermia on cerebral oxygen uptake during gradual cerebral perfusion pressure decrease in piglets

Objective: To study the effect of mild hypothermia on cerebral oxygen metabolism and brain function in piglets during reduced cerebral blood flow because of gradual reduction of the effective cerebral perfusion pressure (CPP). Design: Comparison of two randomized treatment groups: normothermic group (NT; n = 7) and hypothermic group (HT; n = 7). Setting: Work was conducted in the research laboratory of the Institute for Pathophysiology, Friedrich Schiller University, Jena, Germany. Subjects: Fourteen piglets (14 days old) of mixed German domestic breed. Intervention: Animals were anesthetized and mechanically ventilated. An epidural balloon was gradually inflated to increase intracranial pressure to 25 mm Hg, 35 mm Hg, and 45 mm Hg every 30 mins at adjusted mean arterial blood pressures. After determination of baseline CPP (NT, 79 ± 14 mm Hg; HT, 84 ± 9 mm Hg), CPP was reduced to ∼70%, 50%, and 30% of baseline (NT, 38.1 ± 0.5°C; HT, 31.7 ± 0.5°C). Measurements and Main Results: Every 25 mins after the gradual CPP reductions. Mild hypothermia induced a reduction of the cerebral metabolic rate of oxygen (CMRO2) to 50% ± 15% of baseline values (baseline values, 352 ± 99 μmol·100 g−1·min−1) (p < .05). Moreover, the electrocorticogram was altered to a pattern of reduced delta activity (p < .05) but unchanged higher frequency activity. The cerebral oxygen balance in HT animals remained improved until CPP reduction to 50%, indicated by a reduced cerebral arteriovenous difference of oxygen but elevated brain tissue PO2 (p < .05). Further CPP reduction gave rise to a strong CMRO2 reduction (NT, 19 ± 21%; HT, 15 ± 15%; p < .05). However, the high‐frequency band of electrocorticogram was less reduced in hypothermic animals (p < .05). Conclusions: Mild whole body hypothermia improves cerebral oxygen balance by reduction of brain energy demand in juvenile piglets. The improvement of brain oxygen availability continues during a mild to moderate CPP decrease. A loss of the difference in CMRO2 between the hypothermic and normothermic piglets together with the fact that brain electrical activity was less suppressed under hypothermia during severe cerebral blood flow reduction indicates that hypothermic protection may involve some other mechanisms than reduction of brain oxidative metabolism.

Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.

There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism.

A Piglet Model for Evaluation of Cerebral Blood Flow and Brain Oxidative Metabolism during Gradual Cerebral Perfusion Pressure Decrease

A piglet model was developed to study the effect of epidural volume expansion on cerebral perfusion pressure (CPP) by stepwise elevating intracranial pressure (ICP). Mean arterial blood pressure (ABP) was strictly maintained using an extracorporeal ABP controller. Two-week-old piglets (n = 10) were studied by surgically placing an epidural balloon over the right parietal region and gradually increasing the inflation to increase ICP to 25, 35 and 45 mm Hg, maintaining each pressure level for 30 min. Regional cerebral blood flow was measured using the colored microsphere technique, and cerebral oxygen delivery and cerebral metabolic rate of oxygen were calculated at baseline conditions and after reaching ICP levels of 25, 35 and 45 mm Hg. The results showed that this model of epidural volume expansion reproducibly reduces CPP to 70, 50 and 33% of baseline CPP values with elevation of ICP, and that the physiological variables remained stable throughout each increase in ICP. We conclude that the model simulates the effects of an acute intracranial focal mass expansion and is well suited for the evaluation of different therapeutical strategies for increased ICP in newborns and infants.

ONTOGENETIC ASPECTS OF TRAUMATIC BRAIN EDEMA : FACTS AND SUGGESTIONS

Diffuse brain swelling (DBS) after severe traumatic brain injury (TBI) occurs more commonly in children than adults. Most of the recent clinical studies suggest that young children are more negatively affected by DBS. Until now studies in young animals in which the pathophysiology of DBS was evaluated remained seldom. However, pathogenetic mechanisms of edema formation after TBI in the immature brain appeared to be different in comparison to adult brains. There are evidences that vasogenic as well as cytotoxic edema components may be responsible for the development of DBS. Besides mechanical disturbance, the blood-brain barrier seems to be strongly endangered by oxidative stress after TBI because regional antioxidative capacity is obviously diminished. In addition, cytotoxic components of DBS may be caused by at least two different mechanisms. First, it was shown that a sustained posttraumatic cerebral hypoperfusion occurs in the immature brain. Moreover, a transient increase of NMDA receptor expression at this period of life may be responsible for an increased threat of intracellular sodium ion accumulation in brain cells. Obviously, brain swelling can be detrimental because it can elevate intracranial pressure, impair CBF, and may represent ongoing secondary brain injury.