Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction.

BACKGROUND: The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. METHODS: The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. RESULTS: Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). CONCLUSION: After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.

Recirculation usually precedes malignant edema in middle cerebral artery infarcts.

OBJECTIVES: In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 2-5 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue. METHODS: Forty-four patients with malignant MCA infarcts were included after decision to perform decompressive hemicraniectomy (DHC). Cerebral energy metabolism was in all patients monitored bedside by 1-3 microdialysis catheters inserted into the infarcted hemisphere during DHC. In 29 of the patients, one microdialysis catheter was also placed in the non-infarcted hemisphere. MCA blood-flow velocity was monitored bilaterally by transcranial Doppler ultrasound. RESULTS: The interstitial glucose levels were in both sides within normal limits throughout the monitoring period. Mean lactate/pyruvate (LP) ratio was very high in infarcted tissue immediately after DHC. The ratio slowly decreased but did not reach normal level during the study period. In the infarcted hemisphere, MCA blood-flow velocities increased from approximately 42 cm/s 1 day prior to DHC (nine of nine patients) to approximately 60 cm/s at day 4. CONCLUSIONS: Normal interstitial glucose level in the infarcted hemisphere in combination with substantial MCA blood-flow velocities bilaterally even before DHC was performed indicates that malignant brain swelling usually commences when the embolus/thrombosis has been largely resolved and recirculation of the infarcted area has started. The protracted increase of the LP ratio in infarcted tissue might indicate mitochondrial dysfunction.

Active cooling in traumatic brain-injured patients: a questionable therapy?

Hypothermia is shown to be beneficial for the outcome after a transient global brain ischaemia through its neuroprotective effect. Whether this is also the case after focal ischaemia, such as following a severe traumatic brain injury (TBI), has been investigated in numerous studies, some of which have shown a tendency towards an improved outcome, whereas others have not been able to demonstrate any beneficial effect. A Cochrane report concluded that the majority of the trials that have already been published have been of low quality, with unclear allocation concealment. If only high-quality trials are considered, TBI patients treated with active cooling were more likely to die, a conclusion supported by a recent high-quality Canadian trial on children. Still, there is a belief that a modified protocol with a shorter time from the accident to the start of active cooling, longer cooling and rewarming time and better control of blood pressure and intracranial pressure would be beneficial for TBI patients. This belief has led to the instigation of new trials in adults and in children, including these types of protocol adjustments. The present review provides a short summary of our present knowledge of the use of active cooling in TBI patients, and presents some tentative explanations as to why active cooling has not been shown to be effective for outcome after TBI. We focus particularly on the compromised circulation of the penumbra zone, which may be further reduced by the stress caused by the difference in thermostat and body temperature and by the hypothermia-induced more frequent use of vasoconstrictors, and by the increased risk of contusional bleedings under hypothermia. We suggest that high fever should be reduced pharmacologically.

Regional cerebral metabolic rate (positron emission tomography) during inhalation of nitrous oxide 50% in humans.

BACKGROUND: Recent studies in man have shown that cerebral blood flow increases during inhalation of nitrous oxide (N2O), a finding which is believed to be a result of an increased cerebral metabolic rate (CMR). However, this has not previously been evaluated in man. METHODS: Regional CMR(glu) (rCMR(glu)) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(18F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. RESULTS: Global CMR(glu) in young men was 27 (3) micromol 100 g(-1) min(-1) [mean (SD)]. Inhalation of N2O 50% did not change global CMR(glu) [30 (5) micromol 100 g(-1) min(-1)] significantly, but it changed the distribution of the metabolism in the brain (P<0.0001 analysis of variance). Compared with inhalation of O2 30% in N2, N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%, P<0.05] and thalamus [22 (23) %, P<0.05]. There was a prolonged metabolic effect of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air (P<0.0001) performed 1 h after the N2O administration. CONCLUSIONS: Inhalation of N2O 50% did not change global CMR(glu), but the metabolism increased in central brain structures, an effect that was still present 1 h after discontinuation of N2O.

Selective dorsal rhizotomy and postoperative pain management. A worldwide survey.

BACKGROUND: Selective dorsal rhizotomy (SDR) is an operation method that decreases the degree of spasticity with long-lasting beneficial effects for children with spastic diplegia. Children undergoing SDR are postoperatively in severe pain, a pain related to both the extensive surgical exposure with multilevel laminectomy and the nerve root manipulation. Various pain management strategies for children undergoing SDR have been published. The postoperative pain treatment is a vital part of the management. The aim of this study was to estimate the number of centers performing SDR, the frequency of SDR surgery and to investigate pain management of the different centers. METHODS: A questionnaire comprising 7 questions was sent by mail and/or e-mail to a total of 59 potential centers performing SDR, centers that have published material concerning SDR or centers that have been recommended. Forty-seven (80%) centers responded to the questionnaire; 11 of them do not presently perform SDR surgery, and the remaining 36 centers constitute the material of the present study. RESULTS: 23 of the 36 centers use Peacock's operation technique and 8 centers use Park's technique. Continuous intravenous infusion of opioids for postoperative pain treatment is used by 17 (47%) of the centers. Seven (19%) centers use the epidural (ED) approach for treating postoperative pain and 6 (17%) centers use intrathecal (IT) pain treatment. The duration of intravenous ED or IT pain relief ranged from 24 h up to 7 days. To evaluate pain relief, 25 (70%) centers used some form of pain scale. CONCLUSION: The most common operation techniques in use today are described by Peacock or by Park, with an estimated number of procedures of more than 487/year in 36 centers. The majority of the centers seem to have a satisfactory pain management strategy. These centers administer continuous infusions of opioids, with an intravenous, ED or IT approach, and incorporate the use of a pain assessment tool to evaluate pain relief.

Serial S100B levels before, during and after cerebral herniation.

Protein S100B has been shown to increase in serum and cerebrospinal fluid (CSF) in various neurological diseases. However, the levels of S100B in conjunction with cerebral herniation have not been studied and the significance of extracerebral S100B has become an important issue. We report on a multi-trauma patient in whom cerebral herniation occurred 2 days after admission. Following this, organ-harvesting procedures were performed for transplantation. We measured serial serum S100B during both the ongoing herniation and the following extracerebral surgery. We found that S100B levels seemed to peak immediately prior to cerebral herniation and then decreased shortly thereafter and concluded that the source of the measured serum S100B in this patient was of predominately cerebral origin. In conjunction with the organ harvesting procedure S100B levels increased, indicating that extracerebral sources of the protein also exist.

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. METHODS: Ten patients with post-SAH fatigue were investigated with 3D-CBF (SPECT) and underwent an evaluation of the pituitary function. RESULTS: Five had normal pituitary function. Disturbances in the gonadotropin function was detected in three patients and suspected in two. The mean insulin-like growth factor I (IGF-I) value of the patients was in the lower part of the reference range. In the patients with endocrine dysfunction, the 3D-CBF was pathologic in the central structures of the basal region. CONCLUSIONS: The present results indicate that an aneurysmal SAH may result in partially impaired pituitary capacity. This deficit may contribute to fatigue after aneurysmal SAH, but cannot solely explain this disorder. SPECT identified regional tissue damage in the patients with pituitary dysfunction after SAH.

Retrograde intubation with a Mini-Trach II kit.

BACKGROUND: Retrograde intubation has been accepted internationally as a viable alternative for managing the difficult airway. Various techniques have been described to perform this procedure, however, difficulties have arisen on account of problems with suboptimal materials. We therefore describe a retrograde intubation technique using the knife and stiff plastic introducer from a Mini-Trach II set from Portex Ltd (Kent, UK). METHODS: The cricothyroid membrane was identified and using the knife from the mini-trach set, incised longitudinally. The plastic introducer was inserted through the incision and maneuvered out through the mouth providing a guide over which the endotracheal tube was threaded. The technique was evaluated on 20 cadavers and thereafter used in four patients. RESULTS: Mean intubation time in the 20 cadavers was 6.7 s (range 3-10) from incision to removal of the guide. Also, the technique was used successfully in four patients in whom anterograde attempts failed. In one of these patients the retrograde intubation was life saving. CONCLUSION: Retrograde intubation with a stiff curved plastic introducer was rapid and easy in cadavers and in four patients. In emergency situations where conventional intubation fails it may be life saving.

Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage.

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 (133)Xenon) and regional (three-dimensional (99 m)Tc-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 (CDRO(2)) 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 CDRO(2) 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 CDRO(2) of 1.83 ml * 100 g(-1) * min(-1). The brain volume with a CDRO(2) 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 CDRO(2) remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH.

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.

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 (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O 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 N(2)O 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% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) 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% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O 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 x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O 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 Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

One way to ventilate patients during fibreoptic intubation.

Occasionally anaesthesiologists find themselves in situations where ventilation during intubation with a fibreoptic bronchoscope (FOB) is desirable. In order to ventilate the patient during the FOB intubation, we used a 90 degree angle swivel connector, normally used for fibreoptic bronchoscopia in an intubated patient. After a nasotracheal tube is placed with the tip in the oropharynx, ventilation of the patient is possible via this tube by closing the mouth and other nostril. The fibrescopic procedure is done through the right-angle connector with suction port and the tube is used to guide the tip of the FOB to the aditus laryngis. The method has been used in 7 patients who were impossible to intubate with a conventional procedure. In all patients ventilation was possible and intubation was performed in 5 min (range 1-15).

Morphine with or without a local anaesthetic for postoperative intrathecal pain treatment after selective dorsal rhizotomy in children.

Selective dorsal rhizotomy is a surgical procedure with a selective division of posterior spinal nerve rootlets to treat spasticity in children. The extensive surgical procedure with multilevel laminectomies and the nerve root manipulation result in intense pain postoperatively. Two intrathecal (IT) regimes of pain treatment were compared in these children, concerning their pain relief and possible side-effects. In a prospective study, 12 children (3-6 years of age) with six in each group, received either intermittent IT morphine (5 microg x kg(-1) four times a day) or continuous infusion of a mixture of bupivacaine (40 microg x kg(-1) x h(-1)) and morphine (0.6 microg x kg(-1) x h(-1)). Pain score was lower in the bupivacaine/morphine group (0.2 +/- 1.1) compared to intermittent morphine (2 +/- 2.4) on a scale from 0 to 6 (P less than or = 0.0001). Bupivacaine/morphine resulted in a lower, but not significant, difference in pruritus and lower muscle spasm. Haemodynamic and ventilatory parameters did not differ between the groups. Intrathecal continuous infusion of bupivacaine and morphine was superior to intermittent morphine in the treatment of pain after selective dorsal rhizotomy operations.

The Reflector: a new method for saving anaesthetic vapours.

Anaesthesia systems that minimize the use of volatile anaesthetics to reduce cost and pollution are of interest. Closed circuit anaesthesia is the ideal solution, but requires continuous adjustment of fresh gas flow and composition and thus is demanding in routine practice. We describe an alternative system, the Reflector system, which is open in regard to oxygen, nitrogen and N2O, and semiclosed in regard to volatile anaesthetics. The Reflector system is a circle system with a carbon dioxide absorber and an automatic vapour delivery device placed in the inspiratory limb of the circle. A zeolite filter, the Reflector, is placed between the ventilator and the circle. The Reflector functions as a molecular sieve, preventing the volatile anaesthetic from leaving the circle. Isoflurane consumption using the Reflector system in bench tests and an animal study was compared with that of an open system. In bench tests consumption was reduced by 79% and 82%, at a respiratory frequency of 10 and 20 min-1, respectively. The corresponding mean figures from the animal experiment were 65% and 77%.

Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery.

OBJECTIVE: The study was undertaken to measure baseline values for chemical markers in human subjects during wakefulness, anesthesia, and neurosurgery, using intracerebral microdialysis. METHODS: Microdialysis catheters were inserted into normal posterior frontal cerebral cortex in nine patients who were undergoing surgery to treat benign lesions of the posterior fossa. The perfusion rate was 1.0 microl/min during anesthesia/neurosurgery and the early postoperative course and 0.3 microl/min during the later course. Bedside biochemical analyses of glucose, pyruvate, lactate, glycerol, glutamate, and urea were performed before, during, and after neurosurgery. After the bedside analyses, all samples were frozen for subsequent high-performance liquid chromatographic analyses of amino acids. RESULTS: The following baseline values were obtained during wakefulness (perfusion rate, 0.3 microl/min): glucose, 1.7+/-0.9 mmol/L; lactate, 2.9+/-0.9 mmol/L; pyruvate, 166+/-47 micromol/L; lactate/pyruvate ratio, 23+/-4; glycerol, 82+/-44 micromol/L; glutamate, 16+/-16 mmol/L; urea, 4.4+/-1.7 mmol/L. Marked increases in the levels of all chemical markers were observed at the beginning and end of anesthesia/surgery. CONCLUSION: The study provides human baseline levels for biochemical markers that can presently be measured at the bedside during neurointensive care. In addition, some changes that occurred under varying physiological conditions are described.

Effects of propofol on isolated human pial arteries.

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.

Additional colloids have only a minor haemodilutive effect after surgery for aneurysmal subarachnoid haemorrhage.

Haemodilution is commonly used as prophylaxis, as well as treatment for cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). Thirty-six patients operated for aneurysmal SAH were evaluated retrospectively; 24 received haemodilutive therapy and 12 patients, as a control group, received no additional therapy. There was a 'spontaneous' drop in haematocrit by 22% in both groups, and a corresponding drop in haemoglobin by 23% in the treatment group and 19% in the non-haemodiluted group, during the first 4 days after the SAH. After the initial decrease the haematocrit remained stable between 0.28 and 0.33 until day 14 in both groups. The haemodilutive group had only a minor lower haematocrit level during days 8-12 as the additional fluid resulted in increased renal excretion. This minor difference was, however, significant (p < 0.02).