Peter Reinstrup

Assessment of the Lower Limit for Cerebral Perfusion Pressure in Severe Head Injuries by Bedside Monitoring of Regional Energy Metabolism.

Background In patients with severe traumatic brain lesions, the lower limit for cerebral perfusion pressure (CPP) is controversial. The aim of this prospective study was to assess this limit from bedside measurements of cerebral energy metabolism and to clarify whether the penumbra zone surrounding a focal lesion is more sensitive to a decrease in CPP than less-injured areas. Methods Fifty patients with severe head injury were included after evacuation of an intracranial hematoma and/or focal brain contusion. They were treated according to intensive care routine (Lund concept), including continuous monitoring of intracranial pressure. One microdialysis catheter was inserted in less-injured brain tissue (“better” position), and one or two catheters were inserted into the boundary of injured cerebral cortex (“worse” position). Concentrations of glucose, pyruvate, and lactate were analyzed and displayed bedside and were related to CPP (n = 29,495). Results Mean interstitial glucose concentration was unaffected by the level of the CPP within the studied ranges. Increases in lactate concentration (P = 0.0008) and lactate–pyruvate ratio (P = 0.01) were obtained in the “worse” but not in the “better” position at CPP less than 50 mmHg compared with the same positions at CPP greater than 50 mmHg. Conclusions The study results support the view that CPP may be reduced to 50 mmHg in patients with severe traumatic brain lesions, provided that the physiologic and pharmacologic principles of the Lund concept are recognized. In the individual patient, preservation of normal concentrations of energy metabolites within cerebral areas at risk can be guaranteed by intracerebral microdialysis and bedside biochemical analyses.

Effects of Iso- and Hypervolemic Hemodilution on Regional Cerebral Blood Flow and Oxygen Delivery for Patients with Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Summary.Summary. Background: Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed. Method: Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional 133Xenon) and regional (three-dimensional 99 mTc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml. Findings: Isovolemic hemodilution increased global cerebral blood flow from 52.25±10.12 to 58.56±11.73 ml * 100 g−1 * min−1 (p<0.05), but after hypervolemic hemodilution CBF returned to 51.38±11.34 ml * 100 g−1 * min−1. Global cerebral delivery rate of oxygen (CDRO2) decreased from 7.94±1.92 to 6.98±1.66 ml * 100 g−1 * min−1 (p<0.001) during isovolemic hemodilution and remained reduced, 6.77±1.60 ml * 100 g−1 * min−1 (p<0.001), after the hypervolemic hemodilution. As a test of the hemodilution effect on regional CDRO2 an ischemic threshold was defined as the maximal amount of oxygen transported by a CBF of 10 ml * 100 g−1 * min−1 at a Hb 140 g/l which corresponds to a CDRO2 of 1.83 ml * 100 g−1 * min−1. The brain volume with a CDRO2 exceeding the ichemic threshold was 1300±236 ml before intervention. After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206±341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume remained reduced at 1228±347 ml (p<0.05). Interpretation: The present study of controlled isovolemic hemodilution demonstrated increased global CBF, but there was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO2 remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH.

Effects of nitrous oxide on human regional cerebral blood flow and isolated pial arteries.

BackgroundResults from previous studies on the effect of nitrous oxide (N2O) on the cerebral circulation are conflicting. Early reports claim N2O to have no effect whereas recent findings demonstrate a cerebral cortical vasodilatation during N2O inhalation, but the regional cerebral blood flow (CBF) in the subcortical structures is unknown. MethodsRegional CBF was measured three-dimensionally with single photon emission computer-aided tomography after injection of xenon 133 in 8 spontaneously breathing men (mean age 29.6 yr) during normocapnia and hypocapnia with and without inhalation of 50% N2O. 8 isolated human pial arterial segments were mounted in organ baths. The segments were contracted with prostaglandin F2α and subjected to 30% oxygen and 5.6% carbon dioxide in nitrogen or N2O. ResultsNormocapnic young men had a global CBF of 55 ± 4 ml · 100 g−1. min−1. Decreasing end-tidal CO2 tension by 1.3 kPa (9.3 mmHg) reduced CBF uniformly, with a decrease in global CBF to 45 ± 2 ml · 100 g−1. min−1 (P < 0.0001). During normocapnia, inhalation of 50% N2O increased mean CBF to 67 ± 7 ml · 100 g−1. min−1 (P < 0.0001). Inhalation of 50% N2O during hypocapnia increased mean CBF to 63 ± 5 ml · 100 g−1. min−1 (P < 0.0001). During N2O inhalation there was no significant difference in mean CBF between normo- and hypocapnia. However, during hypocapnia, but not during normocapnia, N2O inhalation significantly changed the distribution of regional CBF (P < 0.0001). Compared with hypocapnia without N2O, flow increased through the frontal (143%), parietal (140%) and temporal (133%) regions as well as through insula (151%), basal ganglia (145%) and thalamus (133%). In isolated human pial arteries, addition of N2O changed neither basal tension, nor the contraction elicited by prostaglandin F2α. ConclusionsInhalation of 50% N2O increased global CBF mainly by augmenting flow in frontal brain structures. In contrast, changes in carbon dioxide without N2O affected CBF uniformly in the brain. The uneven change in distribution of the CBF when N2O was added during hypocapnia, the reduced carbon dioxide response, and the lack of effect of N2O on isolated human pial arteries suggest that N2O may increase metabolism in selected brain areas.

Measuring Elevated Intracranial Pressure through Noninvasive Methods: A Review of the Literature.

Elevated intracranial pressure (ICP) is an important cause of secondary brain injury, and a measurement of ICP is often of crucial value in neurosurgical and neurological patients. The gold standard for ICP monitoring is through an intraventricular catheter, but this invasive technique is associated with certain risks. Intraparenchymal ICP monitoring methods are considered to be a safer alternative but can, in certain conditions, be imprecise due to zero drift and still require an invasive procedure. An accurate noninvasive method to measure elevated ICP would therefore be desirable. This article is a review of the current literature on noninvasive methods for measuring and evaluating elevated ICP. The main focus is on studies that compare noninvasively measured ICP with invasively measured ICP. The aim is to provide an overview of the current state of the most common noninvasive techniques available. Several methods for noninvasive measuring of elevated ICP have been proposed: radiologic methods including computed tomography and magnetic resonance imaging, transcranial Doppler, electroencephalography power spectrum analysis, and the audiological and ophthalmological techniques. The noninvasive methods have many advantages, but remain less accurate compared with the invasive techniques. None of the noninvasive techniques available today are suitable for continuous monitoring, and they cannot be used as a substitute for invasive monitoring. They can, however, provide a reliable measurement of the ICP and be useful as screening methods in select patients, especially when invasive monitoring is contraindicated or unavailable.

Cerebrovascular response to nitrous oxide

At the turn of this century both ether and chloroform were used as anaesthetic agents. However, while Sir Victor Horsley, a British neurosurgeon, preferred chloroform (I) , Harvey Cushing believed that ether was a better choice for neurosurgical procedures ( 2 ) . At that time general anaesthesia was frequently associated with brain protrusion, which led de Martel (3) and later Cushing (4) to recommend that neurosurgery should be carried out under local anaesthesia. However, general anaesthesia for neurosurgical procedures was frequently employed. It is uncertain when N 2 0 was introduced in neuroanaesthesia, but in the late 1940s a combination of N20 barbiturates and trichloroethylene was widely used. N 2 0 possesses advantages superior to most other anaesthetics regarding adjustability of anaesthetic depth and speed of recovery, which is vital in the postoperative surveillance of most neurosurgical patients. Furthermore, since N 2 0 was considered physiologically “inert” with only minor effects on cerebral circulation and metabolism, it became a natural component of anaesthetic gas mixtures during neurosurgical procedures. During the past two decades a substantial amount of information has been presented showing adverse effects of N 2 0 on cerebral blood flow (CBF‘) and intracranial pressure (ICP). Experimental studies using both humans and experimental animals have documented increases in CBF (5-7), cerebral metabolism (CMRO,) (5), and ICP (8, 9). The magnitude of these changes has vaned as a consequence of species differences and interactions with other drugs (10, 11). There is, however, an increasing amount of evidence showing that N 2 0 itself has cerebral vasodilating properties. In a recent study using single photon emission computer-aided tomography (SPECT) after injection of ‘33Xenon (12) administration of a 50% N20, 30% O2 and 20% N2 gas mixture to healthy spontaneously breathing volunteers was associated with a 21% increase in global CBF during normocapnia and an almost identical flow level during hypocapnia. An uneven flow distribution was recorded with increased perfusion mainly in the frontal brain structures, including regions anatomically associated with the limbic system. The mechanism responsible for the cerebrovascular response to N 2 0 is still unclear. Some investigators support the concept of increased cerebral metabolism due to a stimulatory effect by N20, leading to cerebral vasodilation. The uneven flow distribution favouring the frontal parts of the brain and other reports suggesting an increased electrocortical activity in the limbic system during N20 inhalation (1 3) are in line with this theory. Another theoretical explanation for the above mentioned observations is that N 2 0 exerts a direct effect on the cerebral arteries caused by a release of endothelium derived relaxing factor (EDRF‘) from vascular sources, or a direct relaxation of arterial smooth muscle via a nitric oxide resembling mechanism. However, these mechanisms of action seem less plausible since N 2 0 does not influence contractions in isolated human pial arteries (1 2 ) . This in vitro observation does not exclude the possibility that N 2 0 causes liberation of vasoactive substances in vivo as proposed for the rat (4) and in isolated perfused canine brain (1 5). On the other hand, liberation of vasoactive substances would presumably lead to a uniform increase in CBF and therefore not fit with the data suggesting an uneven CBF distribution during N20 inhalation. Today, 150 years after the introduction of N20, we must conclude that further studies are most certainly warranted to clarify the effect of N 2 0 on cerebral circulation and metabolism. However, based on our present knowledge, we can no longer support the use of N 2 0 in patients with reduced intracranial compliance.

Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function and 3D-CBF.

Objective – The reason for longstanding fatigue following aneurysmal subarachnoidal hemorrhage (SAH) is still not clarified. The bleed from supratentorial aneurysms is often in the vicinity of the hypothalamus and pituitary gland making an endocrine dysfunction plausible.

Distribution of cerebral blood flow during anesthesia with isoflurane or halothane in humans

BACKGROUND: Halothane and isoflurane have been shown to induce disparate effects on different brain structures in animals. In humans, various methods for measuring cerebral blood flow (CBF) have produced results compatible with a redistribution of CBF toward deep brain structures during isoflurane anesthesia in humans. This study was undertaken to examine the effects of halothane and isoflurance on the distribution of CBF. METHODS: Twenty ASA physical status patients (four groups, five in each) anesthetized with either isoflurane or halothane (1 MAC) during normo- or hypocapnia (PaCO2 5.6 or 4.2 kPa (42 or 32 mmHg)) were investigated with a two-dimensional CBF measurement (CBFxenon, intravenous 133xenon washout technique) and a three-dimensional method for measurement of the regional CBF (rCBF) distribution with single photon emission computer-aided tomography (SPECT; 99mTc-HMPAO). In the presentation of SPECT data, the mean CBF of the brain was defined as 100%, and all relative flow values are related to this value. RESULTS: The mean CBFxenon level was significantly influenced by the PaCO2 as well as by the anesthetic used. At normocapnia, patients anesthetized with halothane had a mean CBFxenon of 40 +/- 3 (SE) ISI units. With isoflurane, the flow was significantly (P < 0.01, 33 +/- 3 ISI units) less than with halothane. Hypocapnia decreased mean CBFxenon (P < 0.0001) during both anesthetics (halothane 24 +/- 3, isoflurane 13 +/- 2 ISI units). The effects on CBFxenon, between the anesthetics, differed significantly (P < 0.01) also during hypocapnia. There were significant differences in rCBF distribution measured between the two anesthetics (P < 0.05). During isoflurane anesthesia, there was a relative increase in flow values in subcortical regions (thalamus and basal ganglia) to 10-15%, and in pons to 7-10% above average. Halothane, in contrast, induced the highest relative flow levels in the occipital lobes, which increased by approximately 10% above average. The rCBF level was increased approximately 10% in cerebellum with both anesthetics. Changes in PaCO2 did not alter the rCBF distribution significantly. CONCLUSIONS: There is a difference in the human rCBF distribution between halothane and isoflurane with higher relative flows in subcortical regions during isoflurane anesthesia. However, despite this redistribution, isoflurane anesthesia resulted in a lower mean CBFxenon than did anesthesia with halothane. (Less)

Value of conventional, and diffusion- and perfusion weighted MRI in the management of patients with unclear cerebral pathology, admitted to the intensive care unit

The aim of our retrospective study was to determine the extent to which diffusion- and perfusion- weighted MRI combined with conventional MRI could be helpful in the evaluation of intensive care unit (ICU) patients who have unknown or unclear cerebral pathology underlying a serious clinical condition. Twenty-one ICU patients with disparity between the findings on brain CT scan and their clinical status were studied. All patients underwent conventional MR and diffusion-weighted imaging and 14 also had MR perfusion studies. Abnormalities were present on diffusion-weighted imaging of 17 of the 21 patients and on perfusion-weighted studies of 7 of 14 patients. The MRI results changed the preliminary/working diagnosis in six patients. In eight other patients, MRI revealed additional pathology that had not been suspected clinically, and/or characterized more closely findings that had already been detected by CT or suspected clinically. MRI showed abnormalities in four of the five patients who had normal CT. MRI findings suggested a negative clinical outcome in all nine patients who subsequently died. MRI findings also suggested positive long-term outcome in five of nine patients who improved significantly as based on Glasgow and extended Glasgow outcome scales. In the three unconscious patients who had normal diffusion- and perfusion-weighted imaging the clinical outcome was good. This study suggests that MRI in seriously ill ICU patients with unclear cerebral pathology can provide information that changes, characterizes, or supports diagnoses and/or prognoses and therefore facilitates further management.

Weight gain during pregnancy does not influence the spread of spinal analgesia in the term parturient.

Background: It is still controversial whether the spread of spinal anaesthesia in pregnancy is influenced by particular physique. Investigation was based on a clinical observation that parturients with a pronounced “pregnant” physique, e.g. generalised oedema and heavy abdomen, tended to develop more cephalad sensory blockades than parturients without these physical signs. Using weight gain during pregnancy as a measure for the physique at term, we aimed to determine whether this parameter influences the distribution of analgesia after subarachnoidal injection of plain bupivacaine.

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O).

Background It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N2O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N2O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N2O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. Methods Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40–50% N2O, and hypocapnia + 40–50% N2O. CBV was measured after 99mTc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. Results Global CBV during normocapnia and inhalation of 50% O2 was 4.25 ± 0.57% of the brain volume (4.17 ± 0.56 ml/100 g, mean ± SD) with no change during inhalation of 40–50% N2O in O2. Decreasing carbon dioxide (CO2) by 1.5 kPa (11 mmHg) without N2O inhalation and by 1.4 kPa (11 mmHg) with N2O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 ± 0.10% of the brain volume per kilopascal (0.26 ± 0.10 ml · 100 g−1 · kPa−1) without N2O inhalation and by 0.35 ± 0.22% of the brain volume per kilopascal (0.34 ± 0.22 ml · 100 g−1 · kPa−1) during N2O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in &Dgr;CBV when CO2 is changed. N2O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or &Dgr;CBV/&Dgr;CO2 in these nine subjects. Conclusions Nitrous oxide inhalation had no effect either on CBV or on the normal CBV–CO2 response in humans.