Minako Ohtani

Delayed hyperemia causing intracranial hypertension after cardiopulmonary resuscitation

OBJECTIVE To clarify whether early or delayed failure of cerebral perfusion after cardiopulmonary resuscitation (CPR) occurs in humans and contributes to secondary brain damage. DESIGN Prospective, repeated-measures study. SETTING Intensive care unit of Hiroshima University School of Medicine. PATIENTS Eight comatose patients who had undergone successful resuscitation from cardiac arrest. INTERVENTIONS All patients underwent transcranial Doppler sonography examination. The intracranial cerebral pressure (ICP) and jugular venous oxygen saturation (SO2) also were continuously monitored in five patients and three patients, respectively. MEASUREMENTS AND MAIN RESULTS In each patient, we measured the mean flow velocity of the middle cerebral artery transcranially and the mean flow velocity of the internal carotid artery, high in the neck, using transcranial Doppler sonography. The pulsatility index for each measurement was also calculated. The first examinations were performed within 4 to 12 hrs of CPR, and repeat examinations were performed approximately every 12 hrs. The initial mean flow velocities of the middle cerebral artery and the initial mean flow velocities of the internal carotid artery were relatively low, with relatively high pulsatility indices. The mean flow velocities of the middle cerebral artery began to increase at 12 to 24 hrs after CPR and peaked 24 to 120 hrs after CPR. A simultaneous increase in mean flow velocities of the internal carotid artery was observed during this period. The pulsatility index in both arteries dropped significantly during peak mean flow velocity of the middle cerebral artery. In six of seven patients with an abnormal increase (> 100 cm/ sec) in peak mean flow velocity of the middle cerebral artery, the ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery was < 3. This value tended to be lower in patients with poor outcomes. An increased mean flow velocity of the middle cerebral artery, with a ratio of < 3 for mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery, was defined as hyperemia. Although the mean flow velocity of the internal carotid artery was not measured, another patient with an abnormal increase in mean flow velocity of the middle cerebral artery revealed a high jugular venous SO2 value of 83.5%, also representing hyperemia. All ICP values were within the normal range 4 to 12 hrs after CPR and tended to increase before peak mean flow velocity of the middle cerebral artery. The two patients with the lowest ratios of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery showed significant increases in ICP after the peak mean flow velocity of the middle cerebral artery. These two patients subsequently developed brain death. CONCLUSIONS Delayed hyperemia occurs in humans after resuscitation from cardiac arrest. Our data suggest that this delayed hyperemia can lead to intracranial hypertension and occasionally acute brain swelling, contributing to a poor outcome. A high mean flow velocity of the middle cerebral artery with a low ratio of mean flow velocity of the middle cerebral artery to mean flow velocity of the internal carotid artery may be predictive of critical hyperemia. As an indirect method of measuring cerebral blood flow transcranial Doppler sonography can be used to adjust treatment for failure of cerebral perfusion after resuscitation.

Hyperaemia prior to acute cerebral swelling in severe head injuries: The role of transcranial doppler monitoring

SummaryAcute cerebrovascular congestion after a closed head injury is significantly related to intracranial hypertension. As an indirect method of cerebral blood flow measurement, transcranial doppler sonography (TCD) provides a rapid and noninvasive assessment of cerebral haemodynamics, including hyperaemic conditions.TCD examinations was serially performed in 35 patients with severe head injury with intact cerebral circulation; i.e. the mean flow velocity (MFV) patterns of the middle cerebral artery (MCA) did not show signs of cerebral circulatory arrest such as systolic spike, to and fro, or no flow. The results showed that the MFV of the MCAs and ipsilateral extracranial internal carotid arteries (ICAs) in 9 of these patients increased sharply and pulsatility index (PI) decreased during 48–96 hours after the injury. This was soon followed by patterns of high intracranial resistance, consistent with elevated intracranial pressure (ICP) in monitored patients and acute brain swelling on repeated computed tomographic (CT) scans. The correlation between increased MFVs, decreased PIs, and cerebral haemodynamic changes leading to acute brain swelling is discussed.The number of patients who ended with severe disability, vegetative state, or death was 66% in this group of 9 patients, compared to only 34% for the 35 patients overall with severe head injury. Though the morbidity and mortality rates largely depend on the primary injury, the presence of acute cerebral swelling aggravate the grave course in these patients. And the ability of TCD to monitor the hyperaemic state prior to oedema should lead us to adjust the therapy in order to minimize the secondary insult related to intracranial hypertension.

The function of the hypothalamo-pituitary axis in brain dead patients

SummaryIn order to find out the function of the hypothalamo-pituitary axis in brain dead patients, pituitary and hypothalamic hormone concentrations were measured and several anterior pituitary releasing tests were carried out in 39 brain dead patients. In addition, cerebral blood flow measurements were simultaneously performed. In almost all cases, the blood concentration of pituitary and hypothalamic hormones were above the sensitivity of the assay. Anterior pituitary releasing tests indicated that efficient functions of the hypothalamus were severely suppressed, while the normal secretory mechanism of the anterior pituitary was partially preserved in brain dead patients. Histological changes of hypothalamic neurons varied from barely detectable ghost cells to nearly normal cells even in the same case. Although, the remaining circulation seemed not to be sufficient enough to maintain integrated hypothalamo-pituitary function, as shown by the examinations of cerebral blood flow, the presence of hypothalamic hormones in the systemic circulation suggests that these hormones were released and carried from the hypothalamus by minimal flow which is preserved even after the diagnosis of brain death.

Cerebral Fat embolism studied by magnetic resonance imaging, transcranial doppler sonography, and single photon emission computed tomography. Case Report

Cerebral fat embolism syndrome is an uncommon complication of trauma. We present a patient who developed cerebral fat embolism syndrome secondary to long-bone fractures. Although computed tomography of the brain failed to show any intracranial lesion, magnetic resonance imaging (MRI) detected scattered, high-signal-intensity lesions on T2-weighted images. 99mTc-d, 1-hexamethyl-propylene amine oxine single photon emission computed tomography (99mTc-HMPAO SPECT) and transcranial Doppler sonography (TCD) demonstrated low cerebral blood flow in the acute stage. MRI, 99mTc-HMPAO SPECT, and TCD correlated well with the clinical course of cerebral fat embolism syndrome.

Cyanide distribution in five fatal cyanide poisonings and the effect of storage conditions on cyanide concentration in tissue.

The cyanide distribution in five fatal cyanide poisonings was analyzed by the pyridine-pyrazolone method using a Conway diffusion cell. In order to study the effect of storage conditions on cyanide concentration in tissue samples, the cyanide concentrations were first measured immediately after collection of the samples at autopsy, then measured again after storage in a refrigerator (4 degrees C) or in a freezer (-20 degrees C) for periods ranging from 1 day to 3 weeks. Concentrations in all but three of the blood samples stored at 4 degrees C or -20 degrees C increased, with concentration ratios based on measurement made before and after storage ranging from 0.71 to 1.46. The concentrations in the liver, kidney, and brain samples either increased or decreased, with ratios of from 0.2 to 8.8. The concentrations in the stomach contents samples decreased rapidly at 4 degrees C, but hardly changed at all at -20 degrees C.

Automated procedure for determination of barbiturates in serum using the combined system of PrepStation and gas chromatography-mass spectrometry.

A system of an automatic sample preparation procedure followed by on-line injection of the sample extract into a gas chromatograph-mass spectrometer (GC-MS) was developed for the simultaneous analysis of seven barbiturates in human serum. A sample clean-up was performed by a solid-phase extraction (SPE) on a C18 disposable cartridge. A SPE cartridge was preconditioned with methanol and 0.1 M phosphate buffer. After loading 1.5 ml of a diluted serum sample into the SPE cartridge, the cartridge was washed with 2.5 ml of methanol-water (1:9, v/v). Barbiturates were eluted with 1.0 ml of chloroform-isopropanol (3:1, v/v) from the cartridge. The eluate (1 microl) was injected into the GC-MS. The calibration curves, using an internal standard method, demonstrated a good linearity throughout the concentration range from 0.1 to 10 microg ml(-1) for all barbiturates extracted. The proposed method was applied to 27 clinical serum samples from three patients who were administrated secobarbital.

Automated preparation and analysis of barbiturates in human urine using the combined system of PrepStation and gas chromatography-mass spectrometry

A system for an automatic sample preparation procedure followed by on-line injection of the sample extract into a gas chromatography-mass spectrometry (GC-MS) system was developed for the simultaneous analysis of seven barbiturates in human urine. Sample clean-up was performed by a solid-phase extraction (SPE) on a C18 disposable cartridge. A SPE cartridge was preconditioned with methanol and 0.1 M phosphate buffer. After loading a 1.5 ml volume of a urine sample into the SPE cartridge, the cartridge was washed with 2.5 ml of methanol-water (1:9, v/v). Barbiturates were eluted with 1.0 ml of chloroform-isopropanol (3:1, v/v) from the cartridge. The eluate (1 microl) was injected into a GC-MS system. The calibration curves, using an internal standard method, demonstrated a good linearity throughout the concentration range from 0.02 to 10 microg/ml for all barbiturates extracted. The proposed method was applied to several clinical cases. The total analysis time for 20 samples was approximately 14 h.

Detection of S-methylfenitrothion, aminofenitrothion, aminofenitroxon and acetylaminofenitroxon in the urine of a fenitrothion intoxication case☆

A 23-year-old male attempted suicide by ingesting approximately 50 ml of 5% fenitrothion emulsion, and vomited soon afterwards. He was admitted to a hospital about 3 h after ingestion. He recovered and was discharged from hospital 3 days after admission. The serum cholinesterase activity (normal range: 175-440 I.U.) was only 29 at 3 h, 32 at 1 day, 59 at 2 days and 75 at 3 days after ingestion. Fenitrothion and its metabolites in the body fluids were extracted by an Extrelut column extraction method, detected by a gas chromatograph equipped with either a hydrogen flame ionization detector or a flame photometric detector, and confirmed by a gas chromatograph-mass spectrometer. Fenitrothion concentration in the blood was 169.5 ng/g at 3 h after ingestion. The half life of blood fenitrothion concentration was found to be about 4.5 h. Fenitrothion metabolites, 3-methyl-4-nitrophenol, aminofenitrothion, aminofenitroxon, acetylaminofenitroxon and S-methylfenitrothion, were detected in the urine samples. All of them except S-methylfenitrothion were detected in the urine samples collected up to 62 h after ingestion. It would appear therefore that fenitrothion poisoning can be determined by detection and analysis of the metabolites in urine even if fenitrothion has not been detected in the blood.

Gas chromatographic determination of cresols in the biological fluids of a non-fatal case of cresol intoxication

A simple and rapid method for analysis of free and conjugated cresols in biological fluids was developed. Prior to and following freeing of the conjugated cresols by acid hydrolysis in a sealed ampoule, free cresols were extracted by Extrelut column extraction, determined by gas chromatography, and confirmed by gas chromatography-mass spectrometry. In a non-fatal case of cresol intoxication a 46-year-old male had ingested about 100 ml of a saponated cresol soap solution. The concentrations of xylenol (2,4- and/or 2,5-dimethylphenol) and p- and m-cresol in the serum sample collected on admission were 15.8 micrograms/g, 43.3 micrograms/g and 73.8 micrograms/g, respectively. The total cresol concentration of 117 micrograms/g in the serum is within the range of fatal concentrations, and it is suspected therefore that the patients recovery was due to adequate therapy alone.

Determination of dimethoate in blood and hemoperfusion cartridge following ingestion of formothion: A case study

A 57-year-old male who had ingested not more than 22 g of formothion was semicomatose on admission to hospital, approximately 1.5 h after ingestion. Dimethoate, a hydrolyzed formothion, was found in blood samples collected from the patient and in the charcoal column in the direct hemoperfusion cartridge which was used 6 to 7.5 h after ingestion. It was extracted and purified by Extrelut column extraction. A gas chromatograph, equipped with a flame photometric detector and a gas chromatograph-mass spectrometer, were used to detect and confirm the presence of dimethoate. The blood dimethoate concentrations which were taken approximately 1.5 and 6 h after ingestion were 21.4 and 12.7 micrograms/g, respectively. A blood dimethoate concentration of 21.4 micrograms/g would appear to indicate a high level of formothion intoxication. The total amount of dimethoate found in the charcoal column used was 15 mg.