In vivo study of the utility of selective intra-arterial injection of thiopental for neuroprotection in reversible cerebral ischemia.

BACKGROUND: Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. PURPOSE: To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. MATERIAL AND METHODS: In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. RESULTS: There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. CONCLUSION: The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.

Thiopental and decompressive craniectomy as last-tier ICP-treatments in aneurysmal subarachnoid hemorrhage: is functional recovery within reach?

The study aimed to investigate the indication and functional outcome after barbiturates and decompressive craniectomy (DC) as last-tier treatments for elevated intracranial pressure (ICP) in aneurysmal subarachnoid hemorrhage (aSAH). This observational study included 891 aSAH patients treated at a single center between 2008 and 2018. Data on demography, admission status, radiology, ICP, clinical course, and outcome 1-year post-ictus were collected. Patients treated with thiopental (barbiturate) and DC were the main target group.Thirty-nine patients (4%) were treated with thiopental alone and 52 (6%) with DC. These patients were younger and had a worse neurological status than those who did not require these treatments. Before thiopental, the median midline shift was 0 mm, whereas basal cisterns were compressed/obliterated in 66%. The median percentage of monitoring time with ICP > 20 mmHg immediately before treatment was 38%, which did not improve after 6 h of infusion. Before DC, the median midline shift was 10 mm, and the median percentage of monitoring time with ICP > 20 mmHg before DC was 56%, which both significantly improved postoperatively. At follow-up, 52% of the patients not given thiopental or operated with DC reached favorable outcome, whereas this occurred in 10% of the thiopental and DC patients.In summary, 10% of the aSAH cohort required thiopental, DC, or both. Thiopental and DC are important integrated last-tier treatment options, but careful patient selection is needed due to the risk of saving many patients into a state of suffering.

Propofol versus sodium thiopentone for the treatment of status epilepticus and refractory status epilepticus in dogs.

AIMS: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. RESULTS: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013). CONCLUSIONS AND CLINICAL RELEVANCE: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.

Successful treatment of severe, treatment resistant GHB withdrawal through thiopental-coma.

BACKGROUND: In patients with gamma-hydroxybutyrate (GHB) use disorder (GUD), withdrawal can have a fulminant course with rapid progression of severe, potentially life-threatening complications. Case: We present a 45-year old man with severe GHB withdrawal, resistant to conventional treatment with pharmaceutical GHB, high doses of benzodiazepines and baclofen. GHB withdrawal finally responded to thiopental-induced coma therapy, with burst suppression pattern on electroencephalography (EEG). The patient fully recovered, without withdrawal or residual neuropsychiatric symptoms. Discussion: To our knowledge, this is the first case report in which barbiturates were used to induce a coma to treat severe, treatment resistant GHB withdrawal. This case suggests barbiturate coma therapy might be considered in severe GHB withdrawal which does not respond to conventional treatment.

Comparison of the efficacy of ketamine- propofol versus sodium thiopental-fentanyl in sedation: a randomised clinical trial.

BACKGROUND: Many sedative regimens have been studied with controversial efficiencies. This study tried to assess the desirable and adverse effects of sodium thiopental-fentanyl (TF) with ketamine-propofol (KP) for procedural sedation and analgesia in the emergency department. METHODS: After signing written consent, patients were enrolled in this randomised double-blind trial to receive either KP or TF to reach the desired sedation level. The respiratory and haemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared. RESULTS: Of the participants, 47 in the KP group and 49 in the TF group were enrolled. The mean and SD scores were 6.91±1.93 and 8.34±1.25 for patients' satisfaction and 7.55±1.54 and 8.65±1.00 for satisfaction of physicians performing the procedures in TF and KP groups, respectively (p=0.000). Moreover, 39 (79.59%) and 18 (38.29%) of patients declared that they had recalled the procedures in the TF and KP groups, respectively (p=0.000). Transient hypoxia was reported in 2.1% and 8.1% in the KP and TF groups leading to perform 4.2% vs 8.1% airway manoeuvres, respectively, without the need for endotracheal intubation or further admission. CONCLUSIONS: KP and TF combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. This study did not detect a difference regarding adverse respiratory or haemodynamic effects. It is estimated that the TF combination can be potent and efficacious with possible low adverse events in procedural sedation.

Intraoperative refractory status epilepticus caused by propofol -a case report.

BACKGROUND: Status epilepticus, when continued despite the administration of two antiepileptic drugs, is called refractory status epilepticus (RSE). The seizure-like phenomenon due to propofol is widely reported in the literature. However, RSE caused by propofol is rare and is a diagnostic dilemma. CASE: A 44-year-old male patient presented with RSE during the intraoperative period and was under general anesthesia on propofol infusion. The seizure was resistant to benzodiazepines and phenytoin. Thereafter, the seizure subsided after the discontinuation of propofol infusion, and the patient was shifted to fentanyl and dexmedetomidine infusion for the maintenance of anesthesia. The postoperative follow-up was uneventful. CONCLUSIONS: This article focuses on the management of intractable intraoperative seizure and highlights the need for the exploration of seizure characteristics caused by propofol.

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury.

BACKGROUND: The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). METHODS: High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 µmol/L. S-thiopental concentrations and administered doses were registered. RESULTS: Seventeen children treated with BCT 2007-2017 with high-resolution data were included; median age 15 (range 6-17) and median Glasgow coma score 7 (range 3-8). Median time from trauma to start of BCT was 44.5 h (range 2.5-197.5) and from start to stop 99.0 h (range 21.0-329.0). Median ICP was 22 (IQR 20-25) in the half hour period before onset of BCT and 16 (IQR 11-20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62-71) and 63 (57-71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1-0.7), in the half hour period 5 h later 0.3 (IQR 0.1-0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2-0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). CONCLUSION: BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.

Febrile convulsions during recovery after anesthesia in an infant with history of MMR vaccination: A case report.

RATIONALE: Seizures are rare during the perioperative period; in most cases, there is a previous history of epilepsy or surgery-associated seizures. Febrile convulsions may occur when the body temperature rises above 38°C; this is the most common cause of seizures in children. Febrile convulsions after general anesthesia in the postanesthetic care unit (PACU) without a past or family history are rare. Some reviews suggest that since anesthesia changes immunity, elective surgery should be postponed three weeks after live vaccination. PATIENT: A 12-month-old female with bilateral hearing loss underwent cochlear implantation under general anesthesia. She did not have any history of convulsions or developmental disorders. However, 1 week before surgery, measles-mumps-rubella (MMR) vaccination was given as a regular immunization. DIAGNOSES: Forty minutes after arrival at the PACU, sudden generalized tonic-clonic movement occurred during recovery and the patient's measured body temperature exceeded 38.0°C. INTERVENTIONS: Thiopental sodium was administered intravenously as an anticonvulsant, and the tonic-clonic movement stopped immediately. Endotracheal intubation was performed to secure the airway, and tepid massage and diclofenac ß-dimethylaminoethanol administration were performed to lower the patient's body temperature. OUTCOMES: There was no further fever and no seizures, and no other neurological deficits were observed until discharge. LESSONS: The anesthesiologist should check the recent vaccination history even if the patient has not developed particular symptoms after vaccination. It is important to know that febrile convulsions may occur in patients who have recently received MMR vaccination.

Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury.

BACKGROUND: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way. MATERIALS AND METHODS: Patients suffering severe traumatic brain injury (sTBI) were treated according to an intracranial pressure (ICP)-targeted therapy based on the Lund concept and randomized to an add-on treatment with prostacyclin or placebo. Inclusion criteria were verified blunt head trauma, Glasgow Coma Score ≤ 8, age 15-70 years, and a first measured cerebral perfusion pressure of ≥ 10 mmHg. Multimodal monitoring was applied. A brain microdialysis catheter was placed on the worst affected side, close to the penumbra zone. Mean (glycerolmean) and maximal glycerol (glycerolmax) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h. RESULTS: Of the 48 included patients, 45 had valid glycerol and PR measurements available. PR was higher in the placebo group as compared to the prostacyclin group (p = 0.0164). There was a positive correlation between PR and the glycerolmean (ρ = 0.503, p = 0.01) and glycerolmax (ρ = 0.490, p = 0.015) levels in the placebo group only. CONCLUSIONS: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.

Dexmedetomidine-assisted drug interviews: an observation in psychiatric setting.

Drug-assisted interviews are an effective tool in the management of various psychiatric illnesses where psychopharmacological, as well as routine psychological interventions, do not prove beneficial. These have most commonly been done by using barbiturates and benzodiazepines that have given favourable results for a long time. However, they carry the risk of respiratory depression and difficulty in maintaining the plane of sedation where the patient is amenable to interviewing. In our experience of drug-assisted interviews with two patients we used intravenous dexmedetomidine, which is being used in anaesthesia practice for conscious sedation or sedation in the intensive care unit. We found dexmedetomidine to be superior to thiopentone in achieving a level of conscious sedation where the patients were amenable for an interview, with no significant adverse events and faster post-anaesthetic recovery.

Predrawn prehospital medications are microbiologically safe for up to 48 hours.

BACKGROUND: Prehospital medical teams are commonly required to administer a range of medications for urgent stabilisation and treatment. The safe preparation of medications during resuscitation requires attention, time and resources, and can be a source of medication error. In our two road and HEMS (Helicopter Emergency Medical Service) prehospital services, medication errors are mitigated by predrawing commonly used medications to set concentrations daily (Hunter Retrieval Service, HRS) or second-daily (CareFlight Sydney, CFS). However, there are no published data confirming that such practice is microbiologically safe. METHODS: A convenience sample of 299 predrawn medication syringes with syringe dwell times up to 48 hours were collected at the end of their operational deployment. Predrawn medication syringes collected for culture were ketamine, midazolam, fentanyl, thiopentone, rocuronium, suxamethonium, metaraminol and normal saline. The samples were incubated and cultured at a tertiary hospital pathology laboratory using best-practice methodology for non-tissue samples. The samples were collected from June 2017 to February 2018. RESULTS: The mean dwell times ranged from 30.7 hours (fentanyl at HRS) to 48.5 hours (rocuronium at CFS). None of the 299 cultured samples yielded significant micro-organisms. One sample of suxamethonium with a syringe dwell time of 34 hours grew Bacillus cereus but was likely a contaminant introduced during sample collection. CONCLUSION: Predrawing of the eight studied medications for urgent prehospital procedures appears to be a microbiologically safe practice with syringe dwell times up to 48 hours.

Recurrent Seizures in 2 Patients with Magnesium Sulfate-Treated Eclampsia at a Secondary Hospital.

BACKGROUND Recurrent seizure in patients with magnesium sulfate-treated eclampsia is very rare and requires meticulous management due to poor prognosis. The development of eclamptic convulsions is considered a preventable obstetric situation. Magnesium sulfate has been the drug of choice in such cases. However, some cases are persistent and need more aggressive treatment. CASE REPORT First case: A 20-year-old, nulliparous woman was referred from a private midwifery practice with history of convulsion, 40 weeks of gestational age (GA), and in the active phase of labor. She had been treated with magnesium sulfate and nifedipine beforehand. Her fetus was tachycardic, so an emergency caesarean section was done and placental abruption was found. The day after the surgery, the patient had recurrent seizures despite receiving a maintenance dose of magnesium sulfate. The patient then received thiopental sodium and remained stable. Second case: A 19-year-old, nulliparous woman came to the hospital with 40 weeks of GA, prolonged premature rupture of the membrane (PROM), preeclampsia, and cephalopelvic disproportion (CPD). An emergency caesarean section was performed. Eighteen hours after surgery, the patient had convulsions despite receiving magnesium sulfate maintenance therapy. We repeated the loading dose of 2 g magnesium sulfate, but the seizures persisted. Hence, midazolam was given and the seizures remained controlled. Both babies were delivered without any significant complications. CONCLUSIONS We report 2 cases of GIP0-0 women with 40 weeks GA who had magnesium sulfate-resistant eclampsia and needed additional anticonvulsant drugs. These cases show the importance of comprehensive management and the need for alternative drugs in eclampsia.

Comparison of etomidate and sodium thiopental for induction during rapid sequence intubation in convulsive status epilepticus: A retrospective single-center study.

PURPOSE: Few outcome data are available about morbidity associated with endotracheal intubation modalities in critically ill patients with convulsive status epilepticus. We compared etomidate versus sodium thiopental for emergency rapid sequence intubation in patients with out-of-hospital convulsive status epilepticus. METHODS: Patients admitted to our intensive care unit in 2006-2015 were studied retrospectively. The main outcome measure was seizure and/or status epilepticus recurrence within 12 h after rapid sequence intubation. RESULTS: We included 97 patients (60% male; median age, 59 years [IQR, 48-70]). Median time from seizure onset to first antiepileptic drug was 60 min [IQR, 35-90]. Reasons for intubation were coma in 95 (98%), acute respiratory distress in 18 (19%), refractory convulsive status epilepticus in 9 (9%), and shock in 6 (6%) patients; 50 (52%) patients had more than one reason. The hypnotic drugs used were etomidate in 54 (56%) and sodium thiopental in 43 (44%) patients. Seizure and/or status epilepticus recurred in 13 (56%) patients in the etomidate group and 11 patients (44%) in the sodium thiopental group (adjusted common odds ratio [aOR], 0.98; 95%CI, 0.36-2.63; P = 0.97). The two groups were not significantly different for proportions of patients with hemodynamic instability after intubation (aOR, 0.60; 95%CI, 0.23-1.58; P = 0.30) or with difficult endotracheal intubation (OR, 1.28; 95% CI 0.23 to 7.21; P=0.77). CONCLUSIONS: Our findings argue against a difference in seizure and/or status epilepticus recurrences rates between critically ill patients with convulsive status epilepticus given etomidate vs. sodium thiopental as the induction agent for emergency intubation.

175 Years of Progress in PTSD Therapeutics: Learning From the Past.

Traumatic stressors have always been a part of the human experience. What is now referred to as posttraumatic stress disorder (PTSD) was first studied in the context of military trauma during the Civil War and World War I but most extensively in World War II. Much of what we know about the medical and psychological management of PTSD has its origins in military psychiatric approaches, and a review of these practices reveals important tenets that should be applied in current treatment for both military and nonmilitary PTSD. These practices include intervention as soon as possible after the traumatic exposure, provision for a safe and supportive therapeutic milieu designed for an individual's relatively rapid return to his or her responsibilities and normal activities, and using a combination of pharmacotherapy and psychotherapy (especially exposure to the traumatic memory). A review of current guidelines for treatment of PTSD reveals that few treatments are endorsed with great certainty, owing in large part to a paucity of clinical trials, particularly of pharmacotherapy. This shortcoming must be addressed to enable translation of promising discoveries in the neuroscience of fear into the therapeutic advances patients need and deserve. [AJP at 175: Remembering Our Past As We Envision Our Future March 1947: Psychiatric Experience in the War, 1941-1946 Brig. General William C. Menninger "Another observation which can be made as a result of our experience, is that if intensive treatment was provided early, in an environment in which the expectation of recovery prevailed, remarkable results were obtained." (Am J Psychiatry 1947; 103:577-586 )].

Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.

Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA)A receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABAA receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological treatment may help to improve our knowledge.

Decompressive craniectomy in traumatic brain injury: usage and clinical outcome in a single centre.

BACKGROUND: Two randomised controlled trials (RCTs) of decompressive craniectomy (DC) in traumatic brain injury (TBI) have shown poor outcome, but there are considerations of how these protocols relate to real practice. The aims of this study were to evaluate usage and outcome of DC and thiopental in a single centre. METHOD: The study included all TBI patients treated at the neurointensive care unit, Akademiska sjukhuset, Uppsala, Sweden, between 2008 and 2014. Of 609 patients aged 16 years or older, 35 treated with DC and 23 treated with thiopental only were studied in particular. Background variables, intracranial pressure (ICP) measures and global outcome were analysed. RESULTS: Of 35 DC patients, 9 were treated stepwise with thiopental before DC, 9 were treated stepwise with no thiopental before DC and 17 were treated primarily with DC. Six patients received thiopental after DC. For 23 patients, no DC was needed after thiopental. Eighty-eight percent of our DC patients would have qualified for the DECRA study and 38% for the Rescue-ICP trial. Favourable outcome was 44% in patients treated with thiopental before DC, 56% in patients treated with DC without prior thiopental, 29% in patients treated primarily with DC and 52% in patients treated with thiopental with no DC. CONCLUSIONS: The place for DC in TBI management must be evaluated better, and we believe it is important that future RCTs should have clearer and less permissive ICP criteria regarding when thiopental should be followed by DC and DC followed by thiopental.

Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli.