Empirical ratio of the combined use of S-ketamine and propofol in electroconvulsive therapy and its impact on seizure quality.

Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders. In certain cases, ECT-associated anaesthesia can be improved by the use of ketofol (i.e., S-ketamine + propofol). We aimed to evaluate the empirical mixing ratio of ketofol in these cases for better clinical implementation. We retrospectively investigated n = 52 patients who received 919 ECT sessions with S-ketamine plus propofol as anaesthetic agents. Several anaesthesia and ECT-related parameters including doses of S-ketamine and propofol were analysed. The mean empirically determined S-ketamine/propofol ratio was 1.38 (SD ± 0.57) for 919 individual ECT sessions and 1.52 (SD ± 0.62) for 52 patients, respectively. The mean relative dose was 0.72 (± 0.18) mg/kg S-ketamine and 0.54 (± 0.21) mg/kg propofol. Higher propofol dose was associated with poorer seizure quality. Seizure quality and time in recovery room were significantly influenced by age. Ketofol could be an option to exploit the advantageous qualities of S-ketamine and propofol, if both doses are reduced compared with single use of S-ketamine or propofol. Patients with poor seizure quality may benefit from lower propofol doses, which are applicable by the addition of ketamine. An empirically determined mixing ratio in favour of ketamine turned out to be preferable in a clinical setting. Recovery time was primarily prolonged by higher age rather than by ketamine dose, which had previously often been associated with a prolonged monitoring time in the recovery room. These new findings could improve electroconvulsive therapy and should be replicated in a prospective manner.

Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study.

BACKGROUND: No candidate biomarkers based on cerebrospinal fluid (CSF) have been identified as prognostic factors in patients with major depression treated with electroconvulsive therapy (ECT), yet. METHOD: Following different underlying hypotheses, we analysed baseline CSF levels of markers of neurodegeneration (tau proteins, ß-amyloids and neurogranin), elements of the innate immune system (interleukin [IL]-6, neopterin, soluble CD14, soluble CD163, migration inhibitory factor and monocyte chemotactic protein 1), endocannabinoids, sphingolipids and Klotho before ECT in patients with depression (n = 12) to identify possible correlations with the clinical antidepressant response to ECT. RESULTS: Correlation with the reduction of the depressive symptoms could be observed especially for markers of neurodegeneration and elements of the innate immune system. Differences for CSF levels of several markers were found between the groups of responders and non-responders at the trend level. LIMITATIONS: The sample size is small and the -distribution of responders and non-responders is uneven. CONCLUSIONS: It is this first study on CSF biomarkers for antidepressant efficacy of ECT warrants further research regarding the mechanism of ECT and personalized antidepressant therapy.

Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study.

Despite the lack of clinical data about the role of the endocannabinoid system (ECS) in affective disorders, preclinical work suggests that the ECS is relevant in both with regard to the etiology of depression as well as the mediation of antidepressant effects. We measured the intraindividual levels of the endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) in the cerebrospinal fluid of 12 patients suffering from a major depressive episode before and after the antidepressant treatment by electroconvulsive therapy (ECT). AEA was significantly elevated after ECT as compared to baseline. The AEA increase positively correlated with the number of individually performed ECT sessions. Although the sample size was small and confounders were not rigorously controlled for, our finding corroborates preclinical work and should encourage further exploration of the involvement of the ECS in depressive disorder.

Alcohol Use Disorder as a Possible Predictor of Electroconvulsive Therapy Response.

INTRODUCTION: Two rapidly acting antidepressive treatment forms, namely, electroconvulsive therapy (ECT) and ketamine, possibly share a common mechanism of action primarily involving alterations of neurotransmission (glutamate and γ-aminobutyric acid levels). Because patients receiving ketamine and with a coexistent family history of an alcohol use disorder (AUD) seem to benefit from consistent and longer lasting antidepressive effects, we hypothesized better treatment response in ECT patients with an own history or a family history of an AUD. METHOD: One hundred forty-one psychiatric inpatients with a major depressive episode, who were treated with ECT, were enrolled into this retrospective study. Age, sex, family or personal history of alcohol or benzodiazepine use disorder, ECT response data, and ECT treatment-related data were collected and analyzed with ordinal logistic regression and Fisher exact tests. RESULTS: Twenty-one percent of all patients had their own history of an AUD, 11% had their own history of a benzodiazepine use disorder, and 11% reported on a positive family history of alcohol or benzodiazepine use disorder. The logistic regression analyses revealed that only patient's own history of an AUD predicts a better ECT response (P = 0.031; odds ratio, 2.1; Fisher exact test, P = 0.006). CONCLUSIONS: Within the limitations of a retrospective study, a history of an AUD seems to be a positive predictor for an ECT response in patients experiencing a major depressive episode, which has not been found in 2 earlier studies. Findings are in line with neurobiological hypotheses of excitatory/inhibitory neurotransmitter changes with ketamine and ECT.

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

Protein S-100 and neuron-specific enolase serum levels remain unaffected by electroconvulsive therapy in patients with depression.

The mechanism of the reversible cognitive deficits that might occur within an electroconvulsive therapy (ECT) treatment has not been clarified in a substantial way yet. Although the data available so far do not point towards a cause due to any structural or diffuse damage, further clarification, especially of the role of S-100 seems to be necessary before robust conclusions can be drawn. Serum levels of protein S-100 and neuron-specific enolase (NSE) were analysed in 19 patients with depression, who received ECT. The sampling was adjusted for the short half-life of protein S-100. Several outcome parameters such as Hamilton Depression Rating Scale and Mini-mental state examination before and after the ECT, response and remission to the treatment were recorded. S-100 and NSE levels at baseline, 30 and 60 min after the third session and after the end of the ECT remained stable. S-100 and NSE levels were neither associated with antidepressant response or remission nor with alterations in the cognitive performance. Although aiming for detecting potential rise in these established brain damage markers, an increase due to ECT was not observed, which is in line with the previous studies concerning the safety of ECT on a cellular basis.

Impact of the anesthetic agents ketamine, etomidate, thiopental, and propofol on seizure parameters and seizure quality in electroconvulsive therapy: a retrospective study.

In electroconvulsive therapy (ECT), the use of anesthetics without relevant anticonvulsant properties such as ketamine and etomidate may be favorable for seizure quality. Since there is a relative paucity of studies devoted to this issue, our aim was to compare different anesthetics for ECT regarding their impact on seizure quality and different seizure parameters. We retrospectively compared ketamine (n = 912 anesthesias), etomidate (n = 227 anesthesias), thiopental (n = 2,751 anesthesias), and propofol (n = 42 anesthesias) on their influence on general seizure quality and different seizure parameters by multivariate repeated measurement regression analyses. The use of ketamine and etomidate as anesthetics led to seizures that were overall higher in quality and also longer in motor seizure activity when compared to anesthesia with thiopental and propofol. Ketamine was most favorable concerning central inhibitory potential that was indirectly quantified by concordance and postictal suppression. The worst seizure quality was observed with propofol anesthesia; further, this substance had a negative impact on autonomic activation and seizure duration. Based on the data of this retrospective study, the use of ketamine or etomidate as anesthetic in ECT might be advantageous due to the induction of high-quality seizures.

New evidence for seizure quality improvement by hyperoxia and mild hypocapnia.

INTRODUCTION: Preoxygenation and hyperventilation (with oxygen) in electroconvulsive therapy (ECT) may improve not only safety but also seizure quality. METHODS: We retrospectively examined transcutaneous tissue partial pressure of oxygen (tcpO2) and carbon dioxide (tcpCO2) in 441 ECT sessions of 37 consecutive patients. All patients received standard face mask airway management. In parallel, seizure quality markers such as seizure duration, seizure amplitude, central inhibition, interhemispheric coherence, and sympathetic activation were documented and used to build up a seizure quality sum score. RESULTS: Mean (SD) tcpO2 was 289 (123) mm Hg and for tcpCO2 41 (11) mm Hg. A multivariate repeated measurement regression analysis revealed that the ratio of tcpO2/tcpCO2 had a significant influence on the seizure quality sum score (P = 0.033). Furthermore, a corresponding regression analysis with charge ("stimulation energy") as a dependent variable showed a significant influence of tcpO2 (P = 0.019) and of tcpO2/tcpCO2 (P = 0.03), too. CONCLUSIONS: We observed, in our typical clinical ECT sample of 37 patients, a significant and synergistic influence of tcpO2/tcpCO2 on seizure quality. Partial pressure of oxygen covaried with lower stimulation energy. The ratio tcpO2/tcpCO2 was associated with lower stimulation energy and still better seizure quality.

Management of severe postictal agitation after electroconvulsive therapy with bispectrum electroencephalogram index monitoring: a case report.

Postictal agitation (PIA) with possible severe implications occurs in approximately 10% of electroconvulsive therapy (ECT) sessions. The pathomechanism is not well understood, and suggested treatments are empirical based. We report a case of repetitive (47/57 sessions [83%]) severe PIA after ECT in a case with severe depression. If the minimal bispectrum EEG index (BIS) value, meaning the deepest level of sedation of the thiopental narcosis dropped below 50, PIA occurred in only 9.1%. Bispectral index (BIS) monitoring made prediction and prevention of PIA possible to some degree. Postictal agitation might occur in vulnerable patients when initial depth of anesthesia is too light.

Electroconvulsive therapy in a patient after radiation treatment of a brain metastasis: a case report.

Major depression has a high incidence in patients with cancer, but treatment guidelines for this vulnerable population are missing and antidepressants seem to be less effective than in patients not affected by cancer. We report the case of a patient with bronchial cancer with a single temporo-occipital brain metastasis that had been treated by radiotherapy (whole-brain radiation, 40 Gy, followed by a stereotactic radiotherapy, 15 Gy). The patient developed a major depressive episode and was successfully treated with electroconvulsive therapy without relevant adverse events. This case further underscores the safety and effectiveness of electroconvulsive therapy after radiotherapy of the brain and demonstrates a viable alternative for severely depressed patients with cancer who do not adequately respond to psychotherapy or pharmacotherapy alone.

Rethinking restimulation: a case report.

The individual time-course of the seizure threshold (ST) in electroconvulsive therapy is mostly unknown. It is assumed that a typical seizure is followed by a short refractory period and that ST increases in the long run. We hypothesize ST to be lowered immediately after the refractory period, particularly after inadequate or abortive seizures where risk for prolonged seizures is generally higher. Ketamine anesthesia does not possess pronounced anticonvulsive properties like propofol, etomidate, thiopental, or methohexital. It is therefore ideal to test such a hypothesis. We report the case of a geriatric patient with a major depressive episode, who received 5 consecutive electroconvulsive therapies with S-ketamine, all with identical right unilateral high-energy stimulation and restimulation. Whereas all primary stimulations were inadequate, all restimulations showed significantly improved seizure parameters such as midictal amplitude, maximal postictal heart rate, and average seizure energy index. In this patient, the refractory period turned out to be longer than 1 minute, and ST was lower in all 5 instances of restimulation. This ST decrease could be clinically useful in one-session restimulations.

Influence of sedation on patients' perceptions and recovery in patients undergoing minor perianal procedures under spinal saddle block.

OBJECTIVES: Additional intra-operative sedation may help improve acceptability and comfort of anaesthesia in patients undergoing minor anorectal (perianal) procedures under spinal saddle block. This observational study was done to determine which patients request sedatives and to what extent sedatives affect the patients' recovery. SUBJECTS AND METHODS: During a 6-month period, 500 patients undergoing minor perianal procedures received 1.0 ml hyperbaric bupivacaine (0.5%). On request, a light sedation with propofol in bolus application was provided. Patients were evaluated postoperatively using a standardized questionnaire about their perceptions before, during and 48 h after the administration of anaesthesia. RESULTS: More female (91/143, 63.6%) than male (136/259, 52.5%) patients (p = 0.0312) received sedation. Patients with sedation were significantly younger (46.7 +/- 13.8 vs. 50 +/- 13.8 years, p = 0.0171) and had a lower body mass index (BMI; 25.6 +/- 4.3 vs. 27.5 +/- 5.1, p < 0.0001). Time to mobilization and first micturition was significantly longer in patients with sedation (4.8 vs. 4.4 h, p = 0.0194 and 5.8 vs. 5.4 h, p = 0.0188), which was associated with a higher incidence of nausea (7.5 vs. 1.7%, p = 0.0083). CONCLUSIONS: Female gender, younger age, lower body weight and lower BMI were associated with higher subjective requirements for sedation. The use of sedation showed prolongation of time to first mobilization and micturition and a higher incidence of nausea.

Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression.

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5pg/ml vs. 991.3pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system-specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder.

Management of Foreign Body Removal in Children by Flexible Bronchoscopy.

BACKGROUND: Rigid bronchoscopy remains the gold standard in many countries to remove airway foreign bodies (FBs). We aimed to analyze the feasibility of airway FB removal in children, primarily by flexible bronchoscopy through a laryngeal mask. METHODS: Between 2008 and 2013, 62 children with suspected airway FB who underwent flexible bronchoscopy were analyzed in a retrospective chart review at a tertiary university hospital with respect to clinical presentation and medical management. RESULTS: In 28/62 children (45.2%) an airway FB could be found and in all patients removed by flexible bronchoscopy. Additional 19/34 children (55.8%), in which no FB was found, showed macroscopic evidence of prior FB aspiration. The most frequently removed airway FBs were nuts (13/28; 46.4%) followed by other organic airway FBs (9/28; 32.2%) and nonorganic airway FBs (6/28; 21.4%). All FBs were uneventfully removed with a grasping forceps (16/28; 57.1%), basket forceps (9/28; 32.2%), suction (2/28; 7.1%), or polypectomy snare (1/28; 3.6%). Children with proven airway FB were significantly younger than children without an airway FB (24 vs. 27 mo). Adjuvant antibiotic therapy was given in 15/28 (53.6%) children with proven airway FB and 13/34 (38.2%) without, steroids in 24/28 (85.7%) and 21/34 (61.8%), respectively. In 6/28 (9.7%) children epinephrine intrabronchial was used to mobilize the airway FB during bronchoscopy. CONCLUSION: In an optimized clinical setting, flexible bronchoscopy can be regarded as a feasible procedure to remove airway FB through a laryngeal mask. Short-term and long-term outcome is favorable.

The "Forgotten" Treatment of Alcohol Withdrawal Delirium With Electroconvulsive Therapy: Successful Use in a Very Prolonged and Severe Case.

OBJECTIVE: Alcohol withdrawal delirium (AWD) is a notorious complication in alcohol withdrawal. Usually, the symptomatic treatment is efficacious; however, some patients show treatment resistance or a prolonged course of AWD. METHOD: We report the case of a patient with a prolonged and severest form of AWD. Even 11 weeks after admission, he received approximately 100 mg diazepam per week to manage the symptoms of withdrawal delirium. RESULTS: A treatment course of electroconvulsive therapy was initiated, which allowed a complete tapering off of benzodiazepines during electroconvulsive therapy without adverse effects. CONCLUSIONS: The reported case might contribute to alternative approaches reserved for severest forms of prolonged AWD.

Dexmedetomidine for the management of postictal agitation after electroconvulsive therapy with S-ketamine anesthesia.

OBJECTIVES: Postictal agitation (PIA) represents one of the most common complications during a modified electroconvulsive therapy (ECT) course. Its clinical management can be challenging especially in cases with poor response to benzodiazepines. Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist acting predominantly in the locus coeruleus, exerts sedative effects without causing relevant respiratory depression. To the best of our knowledge, this is the first study that aimed to assess the impact of dexmedetomidine use with S-ketamine anesthesia on PIA reduction in ECT. PATIENTS AND METHODS: We retrospectively analyzed 7 patients who underwent 178 ECT sessions with S-ketamine anesthesia between June 2011 and July 2015 at the Central Institute of Mental Health Mannheim. In 101 sessions, the patients received dexmedetomidine in combination with S-ketamine anesthesia. The decision for dexmedetomidine use was based on individual clinical presentation (patients with positive PIA history). A multivariate repeated measurement logistic regression analysis was conducted to investigate the effect of dexmedetomidine use on the occurrence of PIA. We hypothesized that the use of dexmedetomidine reduced the incidence of PIA also in combination with S-ketamine anesthesia. RESULTS: The prevalence of PIA in ECT sessions with dexmedetomidine administration was lower (mean per patient, 34% vs 62%). In the multivariate logistic regression analysis, the use of dexmedetomidine predicted the non-occurrence of PIA in a highly significant manner (P=0.001, z=-3.83, odds ratio =0.011-0.303). CONCLUSION: Adjunctive use of dexmedetomidine to S-ketamine anesthesia in ECT seems to be a promising tool for the management of intractable PIA syndrome.

Electroconvulsive therapy selectively enhances amyloid ß 1-42 in the cerebrospinal fluid of patients with major depression: A prospective pilot study.

A complex interplay between ß-amyloid (Aß), Alzheimer׳s disease (AD) and major depression disorder (MDD) suggests that patients with MDD have an altered cerebral Aß metabolism and an increased risk of developing AD. In order to elucidate the relationship between antidepressant treatment and Aß metabolism in humans, we performed a study on Aß peptides in the cerebrospinal fluid (CSF) in patients with MDD during electroconvulsive therapy (ECT) as an effective antidepressant treatment. We measured the levels of Aß1-42, Aß1-40 and of tau proteins in the CSF in 12 patients with MDD before and after a course of ECT. Aß1-42 was significantly elevated after the ECT treatment compared to baseline, whereas no difference was found for other peptides and proteins such as Aß1-40, Aß ratio, total tau protein or its phosphorylated form. The most salient finding was, that the increase of Aß1-42 after ECT was found in all patients with clinical response to the treatment, but not in those who did not respond. The number of ECT sessions of each responding patient correlated with the increase of Aß1-42 in the CSF. Our data point towards to a specific antidepressant mechanism which is not based on a general increase of Aß, but seems to involve merely Aß1-42, the isoform with highest amyloidogenic potential. We present the first study in humans demonstrating an isolated mobilization of Aß1-42 in the CSF of patients with depression who respond to an ECT treatment.

Serum lipid profile changes after successful treatment with electroconvulsive therapy in major depression: A prospective pilot trial.

BACKGROUND: Cholesterol is reduced in depressed patients, however, these patients have a higher risk for cardiovascular diseases. Electroconvulsive therapy (ECT) is a highly effective treatment option for specific forms of depression. Like for other non-pharmacological therapies targeting depression such as psychotherapy or sleep deprivation, there is a lack of evidence about the effects on peripheral lipid parameters. Our objective was to study the impact of ECT as a non-pharmacological treatment on the peripheral lipid pattern in depressive patients. METHOD: Peripheral lipid profile composition before and after a course of ECT was analysed in 27 non-fasting inpatients at a university psychiatric hospital with DSM-IV major depressive episode. For the impact of ECT treatment on each lipid parameter a multivariate repeated measurement regression analysis was performed and computed separately for every dependent variable. RESULTS: Total Cholesterol and the cholesterol subtypes HDL and LDL were increased after the treatment compared to baseline. Apolipoprotein A1 was also increased after ECT, whereas apolipoprotein B was not. Indices for the prediction of cardiovascular diseases were unchanged after successful treatment by ECT. The reduction of depressive psychopathology negatively correlated with increases of HDL cholesterol and apolipoprotein A1. LIMITATIONS: Subjects received several antidepressants and other psychotropic medication before and during the ECT. CONCLUSIONS: In our preliminary pilot study ECT as a non-pharmacological, effective treatment of depression led to distinct effects on the peripheral lipid pattern.