Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100ß from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100ß from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100ß, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation.

BACKGROUND: Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension. METHODS: We monitored intraoperative cerebral perfusion in 50 patients aged 18-40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO2, O2, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium). RESULTS: Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)]. CONCLUSIONS: Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.

Effects of catecholamines on cerebral blood vessels in patients with traumatic brain injury.

Data on the cerebrovascular effects of catecholamines after head injury are difficult both to interpret and to compare. Diverse parameters with regard to brain trauma animal models, methods of determining the effects on the cerebral blood flow and metabolism and choice of end-points have been used. Many studies investigate the cerebrovascular effects of catecholamines over a range of cerebral perfusion pressures above the range recommended by current guidelines. The relationship between patient outcome and the use of a specific substance to improve cerebral perfusion has not been investigated. Dopamine, norepinephrine and phenylephrine all seem to increase cerebral blood flow in various animal models and in patients. The data suggest that norepinephrine may be the most predictable. It is associated with an improved restoration of global and regional oxygenation when compared to dopamine. Dopamine has been associated with an increase in brain oedema. There is further evidence that dopamine has many disadvantages in critically ill patients due to its ability to suppress circulating concentrations of most anterior pituitary-dependent hormones. Both aspects would further discourage its use. Data on phenylephrine are scarce. It has been associated with increased intracranial pressure and a failure to improve cerebral oxygenation despite markedly improved cerebral perfusion pressure. For all other catecholamines and related substances there are insufficient data on the cerebrovascular effects after head injury. This suggests that norepinephrine may be the catecholamine that is the most suitable substance to maintain or restore adequate cerebral perfusion. The data, however, are insufficient to formulate a guideline.

Intracranial pressure in patients with sepsis.

INTRODUCTION: In sepsis the brain is frequently affected although there is no infection of the CNS (septic encephalopathy). One possible cause of septic encephalopathy is failure of the blood-brain barrier. Brain edema has been documented in animal models of sepsis. Aggressive fluid resuscitation in the early course of sepsis improves survival and is standard practice. We hypothesized that aggressive fluid administration will increase intracranial pressure (ICP) and may cause critical reductions in cerebral perfusion pressure (CPP). MATERIALS AND METHODS: Patients with sepsis were investigated daily on up to four consecutive days in the intensive care unit. Mean arterial blood pressure (MAP) and blood flow velocity in the middle cerebral artery were monitored for one hour each day. ICP was calculated non-invasively from MAP and flow velocity data. S-100beta was determined daily. FINDINGS: Fifty-two measurements were performed in 16 patients. ICP could be determined in 45 measurements in 15 patients. Seven patients had an ICP > 15 mmHg and 11 patients had a CPP < 60 mmHg on at least 1 day. We found no significant correlation between ICP and fluid administration, but low CPP was significantly correlated with elevated S-100beta (r = -0.47, p = 0.001). CONCLUSIONS: Further research is needed to determine the role of ICP/CPP monitoring in patients with sepsis.

Recurrent post-partum seizures after epidural blood patch.

There are many causes for headaches after childbirth. Even though postdural puncture headache (PDPH) has to be considered in a woman with a history of difficult epidural anaesthesia, pre-eclampsia should always be excluded as an important differential diagnosis. We report a case with signs of late-onset pre-eclampsia where administration of an epidural blood patch (EBP) was associated with eclampsia. A hypothetical causal relationship between the EBP and seizures was discarded on the basis of evidence presented in this report.

Ultraviolet light downregulates CD95 ligand and TRAIL receptor expression facilitating actinic keratosis and squamous cell carcinoma formation.

Long-term ultraviolet light exposure of human skin epidermis in Caucasians is associated with an increased risk for the development of melanoma and nonmelanoma skin cancers. Ultraviolet radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and apoptosis-preventing molecules. We demonstrate that, beside CD95 ligand, TRAIL and TRAIL receptors also function as important sensors in the human epidermis preserving skin integrity and preventing cell transformation. Ultraviolet irradiation extensively changes the expression pattern of some of these molecules, diminishing their sensor function. In particular, CD95 ligand and to a somewhat lesser extent TRAIL receptors are downregulated upon ultraviolet light exposure. CD95 ligand downregulation is not due to protein degradation as in situ hybridization experiments strongly support a transcriptional regulation. The downregulation of these molecules with sensor function increases the risk that aberrant cells are less efficiently eliminated. This concept is supported by the fact that the expression of these molecules is also low or absent in actinic keratosis, a precancerous state that has developed as the consequence of long-term ultraviolet exposure. Progression to invasive neoplasms is then accompanied by an upregulation of CD95 ligand and a downregulation of CD95 and of the TRAIL receptors. The high expression of CD95 ligand, TRAIL, and FLIP in squamous cell carcinoma may then contribute to the immune escape of the tumor, whereas the lack of expression of CD95 and TRAIL receptors prevents autolysis of the tumor.

Trigeminocardiac reflex during surgery in the cerebellopontine angle.

OBJECT: In different experimental studies authors have analyzed the autonomic responses elicited by the electrical, mechanical, or chemical stimulation of the trigeminal nerve system. The trigeminocardiac reflex (TCR) is a well-recognized phenomenon that consists of bradycardia, arterial hypotension, apnea, and gastric hypermotility. It occurs during ocular surgery and during other manipulations in and around the orbit. Thus far, it has not been shown that central stimulation of the trigeminal nerve can also cause this reflex. METHODS: The TCR was defined as clinical hypotension with a drop in mean arterial blood pressure (MABP) of more than 20% and bradycardia lower than 60 beats/minute. Pre-, intra-, and postoperative heart rate (HR) and MABP were reviewed retrospectively in 125 patients who underwent surgery for tumors of the cerebellopontine angle (CPA), and they were divided into two groups on the basis of the occurrence of the TCR during surgery. Of the 125 patients, 14 (11%) showed evidence of the TCR during dissection of the tumor near the trigeminal nerve at the brainstem. Their HRs fell 38% and their MABPs fell 48% during operative procedures as compared with preoperative levels. After cessation of manipulation, the HRs and the MABPs returned to preoperative levels. Risk factors for the occurrence of the TCR were compared with results from the literature. CONCLUSIONS: The authors' results show the possibility of occurrence of a TCR during manipulation of the central part of the trigeminal nerve when performing surgery in the CPA.

The impact of systemic vasoconstrictors on the cerebral circulation of anesthetized patients.

UNLABELLED: BACKGROUND. The effect of vasoconstrictors on intracerebral hemodynamics in anesthetized patients is controversial. The influence of phenylephrine and norepinephrine on the cerebral circulation was investigated in isoflurane- or propofol-anesthetized patients using transcranial Doppler ultrasonography. METHODS: Forty patients were randomly assigned to have vasoconstrictor tests with norepinephrine or phenylephrine during either isoflurane or propofol anesthesia. Blood flow velocities were simultaneously measured in the middle cerebral artery and ipsilateral extracranial internal carotid artery. Baseline recordings were done during stable anesthesia in a supine position (test 0). A second series of measurements were performed after norepinephrine or phenylephrine had increased mean arterial blood pressure by about 20% (test 1). With maintained norepinephrine or phenylephrine infusion, a final series of results were obtained after the increased mean arterial blood pressure was counteracted by a slightly head-up patient position (test 2). RESULTS: Both vasoconstrictors significantly increased mean flow velocities in the middle cerebral artery (norepinephrine: 43 +/- 11 cm/s to 49 +/- 11 cm/s; phenylephrine: 43 +/- 8 cm/s to 48 +/- 9 cm/s; +/- SD) and internal carotid artery (norepinephrine: 27 +/- 7 cm/s to 31 +/- 8 cm/s; phenylephrine: 27 +/- 9 cm/s to 31 +/- 10 cm/s) in the isoflurane-but not in the propofol-anesthetized patients. In the head-up position, only small and insignificant flow velocity changes were observed in both cerebral arteries independent of the vasoconstrictor or background anesthetic. CONCLUSIONS: The results of the present study indicate that norepinephrine and phenylephrine do not directly affect intracranial hemodynamics in anesthetized patients, but rather that hemodynamic changes observed with vasoconstrictors reflect the effect of the background anesthetic agents on cerebral pressure autoregulation.

Impaired cerebral autoregulation after mild brain injury.

BACKGROUND: Severe head injury may impair cerebral autoregulation, which can increase the risk of secondary neuronal injury. The likelihood of impairment in autoregulation is assumed to be low with mild head injury. We report here the absence of cerebral autoregulation in a patient who suffered a concussion from an automobile accident 6 days earlier. METHODS: The patient participated in a clinical study approved by the institutional human subjects review committee, investigating the dose-effect relationship of anesthetics on cerebral autoregulation. The patient was scheduled to undergo repair of a knee injury suffered during a motor vehicle accident, during which she had a concussion. The screening evaluation revealed no evidence of neurologic disease. The test was to be performed three times in each patient: baseline autoregulation measurements during stable fentanyl-nitrous oxide anesthesia, second and third measurements during low dose and high dose of the anesthetic to which the patient was assigned. Autoregulation was tested by increasing the mean systemic blood pressure from 80 mm Hg-100 mm Hg using a phenylephrine infusion while simultaneously recording flow velocity from a middle cerebral artery using transcranial Doppler ultrasonography. RESULTS: Static autoregulation testing during baseline testing demonstrated complete absence of this homeostatic mechanism and the study was canceled. Repeated testing in the recovery unit after the patient awoke showed identical results. CONCLUSIONS: Trivial mild head injury may result in loss of cerebral autoregulation. A clinical study of a larger series to document the incidence is warranted.

Effects of the valsalva maneuver on cerebral circulation in healthy adults. A transcranial Doppler Study.

BACKGROUND AND PURPOSE: Knowledge is limited about the effects of the Valsalva maneuver on cerebral circulation because of the poor temporal resolution of traditional cerebral blood flow measurements. The purpose of this study was to investigate changes in cerebral blood flow during the Valsalva maneuver and to explore its potential use for the evaluation of cerebral autoregulation. METHODS: Using transcranial Doppler ultrasonography, we simultaneously recorded systemic arterial blood pressure in the radial artery and flow velocities in both middle cerebral arteries in 10 healthy adults during the Valsalva maneuver. Gosling's pulsatility index was calculated for all phases of the Valsalva maneuver. Autoregulatory capacities were estimated from the change in cerebrovascular resistance (flow velocity in relationship to blood pressure) during phase II and changes in the velocity-pressure relationship in phase IV relative to phase I. RESULTS: The characteristic changes in blood pressure (phases I to IV) were seen in all subjects, accompanying distinct changes in cerebral blood flow velocity. The relative changes in mean velocity during phases II and IV were significantly greater than those in mean blood pressure. Compared with the baseline value, velocity decreased by 35% in phase IIa, then rose by 56.5% in phase IV (corresponding changes in blood pressure were -10.2% and +29.8%, respectively). During phase II, the pulsatility and cerebrovascular resistance decreased by 19.9%. The increase in cerebral blood flow velocity in phase IV was significantly higher than in phase I (P < .0004), and there was no corresponding significant difference in blood pressure. CONCLUSIONS: These results demonstrated that in healthy humans the Valsalva maneuver causes characteristic changes in systemic blood pressure as well as in flow velocity in the middle cerebral artery, reflecting the sympathetic and cerebral autoregulatory responses, respectively. Analysis of these changes may provide an estimate of autoregulatory capacity.

Change in cerebral blood flow velocity with onset of EEG silence during inhalation anesthesia in humans: evidence of flow-metabolism coupling?

In eight subjects anesthetized with moderate to high doses of inhalation anesthetics (isoflurane or desflurane) during normocapnia, the onset of electrical silence in EEG was associated with a sudden reduction of blood flow velocity monitored from the middle cerebral artery. The magnitude of this reduction was 38 +/- 11% (mean +/- SD; range 24-44%). The change in EEG always preceded the change in flow velocity by 5-7 s. These observations suggest that some flow-metabolism coupling mechanism is preserved during inhalation anesthesia in humans.

Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia.

BACKGROUND: Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans. METHODS: In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP. RESULTS: Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol. CONCLUSIONS: At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.

Nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane. A transcranial Doppler study.

Nitrous oxide during neurosurgical procedures is almost always given in combination with either volatile or intravenous anesthetics. The modifying influence of such interventions has been studied clinically and in experimental settings; the reported findings, however, are inconsistent. The present study compares the cerebrovascular effects of MAC equivalent concentrations of isoflurane alone and isoflurane plus nitrous oxide. Twenty lumbar laminectomy patients randomized either to receive isoflurane or isoflurane plus nitrous oxide were investigated over a dose range from 0.5 to 1.5 MAC. A transcranial Doppler (TCD) ultrasonography device was used to measure cerebral blood flow velocity (CBFV) in the right middle cerebral artery (MCA) as an index of anesthetic-induced alterations in cerebral blood flow (CBF). A small but marginally significant decrease in CBFV at 1 MAC and no change at 1.5 MAC occurred in the isoflurane anesthetized patients. In contrast, a small but significant increase in CBFV at 1 MAC and a very significant increase at 1.5 MAC occurred in the isoflurane plus nitrous oxide anesthetized patients. Nitrous oxide added to an isoflurane anesthetic regimen is concluded to be a potent vasodilator. In addition, the vasodilating effects of nitrous oxide were not uniform; they progressively increased with an increasing isoflurane concentration.

[Propofol for neuroanesthesia]. / Propofol in der Neuroanästhesie.

The quality, result, and prognosis of neurosurgery relies heavily on the anaesthetic technique. Many different classes of drugs have been used during neurosurgical anaesthesia. This article reviews the use of intravenous (IV) propofol as an alternative to volatile anaesthetic techniques. Anaesthesia requirements for neurosurgical procedures are elaborated upon in the first part of the article. The priority of neuroanaesthesia is to preserve neuronal function by avoiding complications such as hypoxia, hypercarbia, and cardiovascular instability. Thereafter, the chosen anaesthetic technique should minimally interfere with cerebral autoregulation and CO2 responsiveness, while brain relaxation is encouraged by decreasing the cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF). In addition, the anaesthetic technique should be associated with rapid and predictable recovery in the operating theatre in order to allow early evaluation of the surgery. The second part of the article describes IV techniques for neurosurgery as an alternative to volatile anaesthetics, all of which increase CBF, cerebral blood volume, and intracranial pressure (ICP) in a dose-related manner and diminish cerebral autoregulation and interfere with cerebrovascular CO2 reactivity. Nitrous oxide has a stimulant effect on cerebral metabolism and is associated with an increase in CBF. On the other hand, all IV agents except ketamine are associated with decreases in CMRO2 and are cerebral vasoconstrictors. For this reason, it is rational to use them for the induction and maintenance of anaesthesia for neurosurgery as part of a total IV anaesthetic technique. The third part of the article focuses on propofol as the newest representative of IV anaesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ketamine on cerebral blood flow velocity in humans. Influence of pretreatment with midazolam or esmolol.

During normoventilation and 'light', haemodynamically stable, steady-state anaesthesia with isoflurane 0.3%, the effect of ketamine intravenously was investigated in 24 patients randomly assigned to one of the following groups: group 1 (control group) no ketamine, group 2 (ketamine group) ketamine 2 mg.kg-1, group 3 (ketamine/midazolam group) ketamine 2 mg.kg-1 after pretreatment with midazolam and group 4 (ketamine/esmolol group) ketamine 2 mg.kg-1 while maintaining mean arterial blood pressure at a preketamine level with esmolol. Ketamine-induced cerebrovascular changes were measured by means of transcranial Doppler ultrasonography. Control readings in patients without ketamine challenge demonstrated stable cardiovascular and cerebrovascular baseline conditions. Cerebral blood flow velocity and mean arterial blood pressure, however, significantly increased after administration of ketamine without pretreatment. The increase in cerebral blood flow velocity could not be blocked by maintaining mean arterial blood pressure at baseline value with esmolol. In contrast, the effects of ketamine on cerebral blood flow velocity and mean arterial blood pressure were prevented by prior administration of midazolam. The results suggest that ketamine may significantly influence intracerebral haemodynamics via a direct drug effect rather than via a secondary effect due to changes in arterial carbon dioxide and/or mean arterial blood pressure.

Cerebrovascular response to carbon dioxide during sodium nitroprusside- and isoflurane-induced hypotension.

We have examined the cerebrovascular response to carbon dioxide during normotension, sodium nitroprusside (SNP)-induced hypotension and high dose isoflurane-induced hypotension in 10 patients who received a standardized general anaesthetic. Carbon dioxide reactivity was determined by varying PaCO2 between 3.0 and 8.0 kPa and recording simultaneously blood flow velocity from the middle cerebral artery (vmca). The paired vmca-PaCO2 data were analysed using linear regression to determine carbon dioxide reactivity. During hypotension, both high-dose isoflurane and SNP reduced significantly mean absolute (from 17.4 (SEM 2.3) to 13.0 (1.7) and 8.8 (1.3) cm s-1 kPa-1, respectively; P < 0.05) and relative (from 32.5 (3.8) to 23.6 (2.0) and 15.5 (1.3)% kPa-1, respectively; P < 0.05) cerebrovascular reactivity to carbon dioxide. This reduction was greater during SNP-induced hypotension (P < 0.05). We conclude that cerebrovascular reactivity to carbon dioxide was attenuated during isoflurane and SNP-induced hypotension, and that it was better preserved during isoflurane-induced hypotension.

Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression.

We studied cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients. Anaesthesia was induced with propofol 2.5 mg kg-1, fentanyl 3 micrograms kg-1 and vecuronium 0.1 mg kg-1, and a propofol infusion of 250-300 micrograms kg-1 min-1 was used to induce EEG silence. Cerebral pressure autoregulation was tested by increasing mean arterial pressure (MAP) by 24 (SEM 5) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler. Carbon dioxide reactivity was tested by varying PaCO2 between 4.0 and 7.0 kPa and recording vmca simultaneously. Although absolute carbon dioxide reactivity was reduced, relative carbon dioxide reactivity was within normal limits for all patients studied (mean 8.5 (SEM 0.8) cm s-1 kPa-1 and 22 (2)% kPa-1, respectively). No significant change in vmca (34 (2) and 35 (2) cm s-1) was observed with the increase in MAP (77 (4) to 101 (4) mm Hg) during autoregulation testing. We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remain intact during propofol-induced isoelectric EEG.