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Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data.

PURPOSE: (1) Identify clinical factors that can be used to predict survival in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy regimens, and (2) build a clinical model to predict survival in this patient population. PATIENTS AND METHODS: Using data from two randomized, phase III Eastern Cooperative Oncology Group (ECOG) trials (E5592/E1594), we performed univariate and multivariate stepwise Cox regression analyses to identify survival prognostic factors. We used 75% of randomly sampled data to build a prediction model for survival, and the remaining 25% of data to validate the model. RESULTS: From 1993 to 1999, 1,436 patients with stage IV or IIIB NSCLC with effusion were treated with platinum-based doublets (involving either paclitaxel, docetaxel, or gemcitabine). The response rate and median survival time were 20% and 8.2 months, respectively. One- and 2-year survivals were 33% and 11%, respectively. In multivariate analysis, six independent poor prognostic factors were identified: skin metastasis (hazard ratio [HR], 1.88), lower performance status (ECOG 1 or 2; HR, 1.46), loss of appetite (HR, 1.62), liver metastasis (HR, 1.32), >/= four metastatic sites (HR, 1.20), and no prior surgery (HR, 1.16). A nomogram using six pretreatment prognostic factors was built to predict 1- and 2-year survival. CONCLUSION: Six pretreatment factors can be used to predict survival in chemotherapy-naive NSCLC patients treated with standard chemotherapy. Using our prognostic nomogram, 1- and 2-year survival probability of NSCLC patients can be estimated before treatment. This prognostic model may help clinicians and patients in clinical decision making, as well as investigators in research planning.

Aged↗

Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.

PURPOSE: To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS). PATIENTS AND METHODS: Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks. RESULTS: Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms. CONCLUSION: CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.

Administration, Oral↗

Delayed vasodilation and altered oxygenation after cerebral ischemia in fetal sheep.

The study investigated the hypothesis that delayed cerebral injury after transient cerebral ischemia is associated with vasoconstriction and decreased cerebral oxygenation. Eight chronically instrumented, late gestation fetal sheep were subjected to 30 min of cerebral ischemia in utero. Cortical impedance (CI) and electrocorticogram (ECoG) were recorded to determine the time course of cellular dysfunction. Histologic outcome was assessed 4 d postischemia. Changes in cerebral vascular tone and oxygenation were observed during and for 4 d after the insult using near infrared spectroscopy to measure changes in total cerebral Hb ([tHb]), oxyhemoglobin ([Hbo2]), and oxidized cytochrome aa3 ([Cyto2]). Results are expressed as mean +/- SEM. CI increased transiently during ischemia; then a delayed increase commenced 17.5 +/- 2.3 h postischemia and peaked at 42.3 +/- 2.4 h. ECoG was depressed during and after the insult. Seizures started 13.6 +/- 3.0 h postinsult and persisted for 25.4 +/- 3.2 h. Increases in [tHb] indicated two periods of cerebral vasodilation: immediately after early reperfusion, lasting 2.3 +/- 0.4 h and peaking to 20 +/- 2.0 mumol.L-1; and a later phase, commencing 12.8 +/- 2.0 h postischemia, peaking to 43 +/- 4.0 mumol.L-1 and lasting 43.1 +/- 5.2 h. [Hbo2] was relatively elevated (18 +/- 3.0 mumol.L-1) during d 4 postischemia, demonstrating a delayed increase in mean cerebral oxygen saturation. [Cyto2] fell during the insult (-0.7 +/- 0.2 mumol.L-1); and, commencing at 28-30 h postischemia, fell progressively to reach a minimum of -5.0 +/- 2.8 mumol.L-1 at 78-80 h postischemia. A greater fall in [Cyto2] was related to worse cerebral injury (p < 0.05). Delayed cerebral injury is accompanied by vasodilation and increased mean cerebral oxygen saturation, although a progressive fall in [Cyto2] might indicate a fall in mitochondrial oxygenation, cell loss, or changes in tissue optical characteristics.

Animals↗

Effect of isoflurane and enflurane on the electrocorticogram of epileptic patients.

We studied the effect of inhaled anesthetic agents on the electrocorticogram (ECoG) in four epileptic patients during nondominant right hemisphere temporal lobectomy while they received 70% nitrous oxide in oxygen (70% N2O/O2) alone, 70% N2O/O2 with 0.5 to 1.5% isoflurane, or 70% N2O/O2 with 2% enflurane. The mean frequency of epileptiform spikes decreased during use of isoflurane, but not enflurane, compared with use of 70% N2O/O2 alone. Enflurane produced paroxysms of synchronous high-voltage spikes. The mean number of electrodes exhibiting spike activity decreased with isoflurane use and increased with enflurane use compared with use of 70% N2O/O2 alone. This preliminary study suggests that isoflurane can suppress epileptogenic tissue and that both isoflurane and enflurane can distort the ECoG, confounding accurate identification of the seizure focus. When used judiciously, however, enflurane may be a potent synchronizer and activator of the epileptogenic focus, making it easier to identify.

Action Potentials↗

The prognostic value of residual spikes in the postexcision electrocorticogram after temporal lobectomy.

We correlated the postresection electrocorticograms (ECoGs) of 80 patients who underwent temporal lobectomy under general anesthesia for treatment of intractable complex partial seizures with surgical results in three groups: seizure/aura free (32 patients), auras only (16 patients), and one or more postoperative seizures (32 patients) at mean follow-up times of 34, 31, and 38 months, respectively. Spontaneous "residual spikes," ie, present after all resections, were present in 47% of patients who had no postoperative seizures or auras. However, they occurred in 72% of patients with any postoperative seizures (p less than 0.05). The location (convexity, mesial, or edge of resections) or the distribution (unifocal versus multifocal) of the residual spikes was not of prognostic value. Quantitative studies in 5-minute epochs of the postexcision ECoGs did not reveal a significant difference in the morphology of the residual spikes, ie, the amplitude or firing pattern (single versus polyspike), in the three groups. The group with postoperative seizures showed a higher number of spikes per epoch (greater than or equal to 50), but it was not significant. Although the study shows that patients with residual spikes may have good prognosis, they are at significantly higher risk for postoperative seizures as compared with those without residual spikes. The possibility that intensity of firing of residual spikes may be an additional predictor of outcome warrants further study.

Cerebral Cortex↗

Focal suppression-burst on electrocorticography after temporal lobectomy.

Of 40 patients with cortical resections for epilepsy, three had focal suppression-burst (S-B) on postresection intraoperative electrocorticography (ECoG). Eighteen to 24 months later, two patients were seizure-free and one had rare seizures. Follow-up neuropsychological testing and MRI did not reveal unexpected postoperative abnormalities. Follow-up scalp surface EEGs did not show S-B. Although S-B on postresection ECoG suggests severe localized cortical damage, this pattern near anterior temporal lobectomy resection margins was not associated with postoperative deficits.

Cerebral Cortex↗

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Brain Mapping↗

[Pharmacological studies on human urinary kallidinogenase (SK-827): cerebral protective effects].

We investigated the cerebral protective effects of human urinary kallidinogenase (SK-827) in rabbits. The following results were obtained: 1) At a dose of 5.0 x 10(-3) to 1.25 x 10(-2) PNA U/kg, SK-827 significantly inhibited the decrease of focal cerebral blood flow and the impairment of electrocorticogram (ECoG) activity in infarcted rabbits. 2) SK-827 at a dose of 2.5 x 10(-3) PNA U/kg inhibited the development of infarction area induced by internal carotid arterial injection of glass beads. 3) SK-827 at a dose of 2.5 x 10(-3) to 5.0 x 10(-3) PNA U/kg inhibited the decrease of cerebral cortical pO2 induced by 5% oxygen inhalation. 4) On subacute phase 7 days after the destruction of internal capsule, SK-827 at a dose of 1.25 x 10(-2) PNA U/kg improved the abnormality of spontaneous ECoG. These findings suggest that SK-827 minimizes the reduction of cerebral function induced by ischemia.

Animals↗

[Effect of nizofenone on pyramidal response, electrocorticogram and regional cerebral blood flow following recirculation after complete global brain ischemia in cats].

Effect of nizofenone on pyramidal response (PR), electrocorticogram (ECoG) and regional cerebral blood flow (rCBF) following recirculation after complete global brain ischemia was compared with that of pentobarbital in gallamine-immobilized cats. The basilar artery and the branches of both carotid arteries (superior thyroid artery, dorsal muscular branch, internal carotid artery, occipital artery and ascending pharyngeal artery) were all ligated. The cats were subjected to complete brain ischemia by occluding both common carotid arteries for 45 min, followed by 180 min recirculation. rCBF of the cortex (suprasylvian gyrus) and the internal capsule was monitored by the hydrogen clearance method. Blood gases were regulated within a range determined previously in freely-moving cats throughout the experiment. Nizofenone (1 mg/kg, i.v.) facilitated the recovery of PR and ECoG, and it inhibited the phenomenon of secondary suppression evidenced by interruption and reversion of the recovery process. rCBF showed good recovery throughout the recirculation period. Pentobarbital (20 mg/kg, i.v.) facilitated the recovery of PR during the early period of recirculation, but secondary suppression of PR, associated with the decline of rCBF, was evident. These results suggest that the ameliorative effect of nizofenone on the recovery of neuronal functions is due to its ability to protect neurons against ischemic anoxia and to prevent interruption of postischemic circulation, and also the good recovery of rCBF is due to its ability to protect vasculature against ischemic anoxia.

Animals↗

Effects of L-arginine on penicillin-induced epileptiform activity in rats.

It has been suggested that nitric oxide (NO) is involved in the pathophysiology of epilepsy. Data are, however controversial because it is not clear whether NO has pro- or anticonvulsant effects. The aim of this study was to investigate the effects of NO on penicillin G-induced epileptiform activity. The left cerebral cortex was exposed by craniotomy in urethane-anesthetized Wistar rats. The epileptic activity was produced by intraperitoneal injection of penicillin G (3 million U/kg, i.p.). The ECoG (electrocorticogram) activity was displayed on a four-channel recorder. At 39.7 +/- 5.4 min after penicillin administration, large amplitude sharp waves appeared in the ECoG. Mean spike frequency and mean spike amplitude were calculated as 29.5 +/- 3.2/min and 865 +/- 91 microV, respectively, at the 55th min. 7-Nitroindazole (60 mg/kg, i.p.) injection 30 min before penicillin G administration significantly reduced the latency of epileptiform activity. Intracerebroventricular administration of L-arginine (300 microg/2 microl, i.c.v.) and sodium nitroprusside (100 microg/2 microl, i.c.v.) suppressed epileptiform activity. Saline (2 microl) and D-arginine (300 microg/2 microl, i.c.v.) administration into the cerebral ventricle were completely ineffective on epileptiform activity (P<0.01). These findings suggest that NO may be an endogenous antiepileptic substance.

Action Potentials↗

Summating potential in Meniere's disease.

This study assesses several electrocochleographic (ECoG) duration and amplitude measures in a clinically defined Meniere's group and compares the results with those from a normal hearing control group and a hearing loss group (cochlear). The summating potential (SP)/action potential (AP) amplitude ratio was the most efficient diagnostic measure, with 62% of the Meniere's group demonstrating abnormal ratios compared to 4% of the normal control group and 17% of the cochlear group. The SP changes were then studied from three angles: 1. Comparison of SP changes with glycerol test results; 2. Comparison of ECoG results before and after shunt surgery; and 3. Recording of SP's in guinea pig ears in which hydrops had been created by obliterating the endolymphatic duct.

Action Potentials↗

Eastern Cooperative Oncology Group experience with chemotherapy in advanced non-small cell lung cancer.

Eastern Cooperative Oncology Group (ECOG) investigators have tested a variety of single-agent and combination regimens in patients with non-small cell lung cancer (NSCLC) during the last 2 decades. The following observations have been made. (1) The mitomycin/vinblastine/cisplatin regimen produced a trend for higher response rates in two studies and a significantly higher response rate in a third study. Survival, however, tended to be shorter in patients receiving this regimen. (2) Carboplatin produced a 9% overall response rate and a median survival of 31.7 weeks, which was slightly but significantly longer than the median survivals obtained with three combination chemotherapy regimens. (3) Paclitaxel produced an overall response rate of 21% and a 1-year survival rate of 40% in previously untreated NSCLC patients. This observation led to a phase III trial in which paclitaxel (135 mg/m2 and 250 mg/m2) was combined with cisplatin and compared with etoposide/cisplatin. Response rates for each of the paclitaxel/cisplatin regimens (26% for 135 mg/m2 paclitaxel and 31% for 250 mg/m2) were significantly higher than the response rate for etoposide/cisplatin (12%), but response between the two paclitaxel/cisplatin arms was not significantly different. At this point, there is a trend toward longer survival in each of the paclitaxel/cisplatin arms, but the final survival analyses have not been completed. In the next phase III trial, ECOG will evaluate paclitaxel (135 mg/m2) plus cisplatin in comparison to three other regimens--docetaxel/cisplatin, gemcitabine/cisplatin, and carboplatin/paclitaxel.

Antineoplastic Agents↗

Outpatient pleurodesis of malignant pleural effusions using a small-bore pigtail catheter.

STUDY OBJECTIVE: Patients with symptomatic malignant pleural effusion are usually treated with large-bore chest tube placement and pleurodesis requiring > or = 3 days of hospitalization. We sought to demonstrate the feasibility of ambulatory drainage and sclerosis using a small-bore pigtail catheter in patients with malignant pleural effusions. We reasoned that this approach would improve symptoms and quality of life at a reduced cost. METHODS: A 14F pigtail catheter was percutaneously inserted into the pleural space and connected to a closed gravity-drainage bag system. The patients were instructed in the use of the drainage system and discharged to return for sclerosis with 4 g of talc after the drainage was < 100 mL/24 h. Patients were graded for dyspnea and performances status using the Eastern Cooperative Oncology Group score (ECOG) and baseline and transitional dyspnea index score (BDI-TDI) before tube placement and again at 30 days. Radiographic response was graded as total response, partial response, or failure. Telephone follow-up was initiated when the patient could not return for evaluation. RESULTS: Ten ambulatory women, ages 41 to 79 years, were enrolled. The chest tube was left in place from 1 to 10 days, draining a mean of 2,956 mL (1,685 to 6,050 mL). Only two patients were unable to undergo sclerosis owing to catheter dislodgment and minimal drainage. Six reported symptomatic improvement at 30 days confirmed by TDI and ECOG scores in four of six. One with a prior history of a lobectomy was found to have a chylous pleural effusion and experienced a hydropneumothorax, for which sclerosis was unsuccessful. One died in hospital on day 26 after sclerosis despite radiographic resolution. Of the four patients who had improved dyspnea and functional status by TDI and EGOG scores, radiographic response was complete in three and partial in one. Two of the six were not able to return for follow-up because of weakness but reported improvement by telephone inquiry. CONCLUSION: Ambulatory sclerosis of malignant effusion using a small-bore catheter is a feasible alternative to inpatient sclerosis with a large-bore chest tube, especially in patients with strong preferences for outpatient care.

Adult↗

A comparison of systemic versus inhaled recombinant IL-2 administration for the treatment of metastatic renal cell carcinoma.

The aim of the current study was to compare the objective response and survival rates of patients with mRCC treated with IL-2 administered either systemically (SYST, subcutaneously) or via inhalation (INH), using relatively large sample sizes to afford a more meaningful comparison. We used univariate and multivariate analyses to retrospectively evaluate the data from two different databases generated from 277 patients treated with IL-2 during the 1993-1997 period, one developed at the University Hospital Hamburg-Eppendorf, and the other at Chiron-Amsterdam. Patients treated with INH IL-2 tended to have a poorer ECOG performance status than patients receiving SYST IL-2. Of 75 patients receiving INH IL-2, eight (10.7%) achieved an objective response; of 202 patients administered SYST IL-2, 45 (22.2%) achieved an objective response. The median survival time was 13.8 months for patients receiving INH IL-2 and 13.1 months for patients treated with SYST IL-2. One- and two-year survival rates were also comparable for the two treatment modalities (one-year: INH, 55%; SYST, 56%; two-year: INH, 28%; SYST, 26%). There was no significant difference in the likelihood of survival for patients receiving INH IL-2 versus SYST IL-2 (risk ratio = 0.82, P = 0.27). Patients administered INH IL-2 experienced considerably less toxicity and complications than patients administered SYST IL-2. We conclude that INH IL-2 treatment is at least as effective as SYST IL-2 treatment in promoting the survival of patients with mRCC. Given that INH IL-2 treatment of patients with a poorer ECOG performance status elicited a survival rate comparable to that seen with SYST IL-2 treatment of patients with a superior performance status, the potential exists for INH IL-2 treatment to be even more effective for patients having a better performance status. Additionally, INH IL-2 treatment is considerably less toxic and associated with fewer complications than SYST IL-2 treatment, thus providing a therapeutic option for otherwise untreatable patients, offering patients a relatively good quality of life, and requiring fewer co-medications. Nonetheless, selection of an IL-2 treatment modality should be based on several patient-related considerations. Moreover, these two IL-2 treatment modalities need not be mutually exclusive.

Administration, Inhalation↗

High-frequency gamma-band activity in the basal temporal cortex during picture-naming and lexical-decision tasks.

Gamma-band activity (GBA) in electroencephalograms (EEGs) has been shown to reflect various cognitive processes. GBA has typically been recorded in the 30-60 Hz range in scalp EEGs. Recently, task-related "high GBA" (HGBA) with frequencies up to 100 Hz has been observed in studies with invasive electrocorticograms (ECoGs). In the present study, we recorded ECoGs from the bilateral basal temporal cortices in a patient with epilepsy and evaluated the task-related HGBA (most prominently in the 80-120 Hz range) accompanying picture-naming and lexical-decision tasks. We examined picture naming using two categories (line drawings of animals and tools). The lexical-decision task was performed using words and pseudowords of two distinct Japanese writing forms, kanji (morphograms) and kana (syllabograms). Task-related HGBA was observed bilaterally during the naming task. Recordings from some electrodes revealed significant differences in HGBA between animal and tool pictures. In contrast to the naming task, there was apparent left dominance in the lexical-decision task. Furthermore, significant differences in HGBA were observed between the Japanese kanji and kana words and between the kanji words and kanji pseudowords. A number of differences in the HGBA observed in the recordings from the basal temporal area were consistent with previous findings from neuroimaging and patient studies and suggest that HGBA is a good correlate of visual cognitive functions.

Acoustic Stimulation↗

Insular epilepsy. Similarities to temporal lobe epilepsy. Case report.

Insular epilepsy has been rarely reported and its clinical and electrographic features are poorly understood. The electrographic study of the insula is difficult since it is hidden from the brain surface by the frontal and temporal lobe. A 48 years-old woman started having simple partial autonomic and complex partial seizures with automatisms and ictal left arm paresis 8 years prior to admission. Seizure's frequency was 1 per week. Pre-operative EEG showed a right temporal lobe focus. Neuropsychological testing disclosed right fronto-temporal dysfunction. MRI showed a right anterior insular cavernous angioma. Intraoperative ECoG obtained after splitting of the sylvian fissure showed independent spiking from the insula and temporal lobe and insular spikes that spread to the temporal lobe. The cavernous angioma and the surrounding gliotic tissue were removed and the temporal lobe was left in place. Post-resection ECoG still disclosed independent temporal and insular spiking with a lower frequency. The patient has been seizure-free since surgery. Insular epilepsy may share many clinical and electroencephalographic features with temporal lobe epilepsy.

Brain Neoplasms↗

Results of surgery in patients with bilateral independent temporal lobe spiking (BITLS) with normal MRI or bilateral mesial temporal sclerosis (MTS) investigated with bilateral subdural grids.

PURPOSE: The introduction of new technologies in the clinical practice have greatly decreased the number of patients submitted to invasive recordings. On the other hand, some patients with refractory temporal lobe epilepsy have normal MR scans or bilateral potentially epileptogenic lesions. This paper reports the results of invasive neurophysiology and surgical outcome in such patients. METHOD: Sixteen patients were studied. Eleven had normal MRI (Group I) and five had bilateral mesial temporal sclerosis (Group II). All patients had BITLS and non-localizatory seizures on video-EEG monitoring. All patients were implanted bilaterally with 32-contacts subdural grids. They were submitted to a cortico-amygdalo-total hippocampectomy at the side defined by chronic electrocorticography (ECoG). RESULTS: In Group I, seizures came from a single side in nine patients. In nine patients, seizures started at one side, spread to the ipsolateral contacts and contralaterally afterwards. On the other hand, in two Group I patients seizures started in one mesial region and spread to the contralateral parahippocampus and neocortex before spreading to ipsolateral contacts. All patients in Group II had seizures starting unilaterally with focal EcoG onset in the mesial regions. Eight Group I patients are seizure-free and three are in Engel's class II. Eighty percent of Group II patients are seizure-free after surgery and one patient is in Engel's class II. CONCLUSION: Good surgical results can be obtained in patients with BITLS. Patients with normal MRI seem to have a worse prognosis when compared to patients with unilateral or even bilateral MTS. Extensive subdural coverage is essential in patients with normal MRI.

Adult↗

Appearance of abnormal electrocorticogram patterns during umbilical cord compression in sheep fetus.

A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.

Acidosis↗