Joachim Nadstawek

A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

Background: Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised, double‐blinded study evaluated the analgesic efficacy of prolonged‐release (PR) oral oxycodone when co‐administered with PR oral naloxone, and its impact on opioid‐induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone.

Transcranial High-frequency Repetitive Electrical Stimulation for Recording Myogenic Motor Evoked Potentials with the Patient under General Anesthesia

OBJECTIVE To demonstrate the feasibility of transcranial high-frequency electrical stimulation with the patient under general anesthesia with propofol and alfentanil. This method may be a useful tool for intraoperative monitoring of the motor pathways during cerebral and spinal operations. METHODS A short train from one to eight monopolar anodal electrical pulses was applied transcranially to the motor cortex with a frequency from 100 to 500 Hz in 10 patients. Myogenic motor evoked potentials (MEPs) were recorded from forearm flexor muscles, thenar, and hypothenar. Amplitude and latency of MEPs were evaluated after different stimulation parameters. This combination of anesthetic and transcranial stimulation technique allows recording of myogenic MEPs during general anesthesia, which was found not to be possible with single pulse transcranial stimulation. RESULTS To elicit myogenic MEPs from the target muscles, stimulation had to be applied within the following parameters: minimum threshold intensity was 60 mA for forearm flexor and thenar and 80 mA for hypothenar; minimum number of pulses was two for forearm flexor muscles and thenar and three for hypothenar; minimum stimulation frequency was 200 Hz for thenar and hypothenar and 100 Hz for forearm flexor muscles. CONCLUSION Transcranial high-frequency repetitive electrical stimulation seems to be a new method for monitoring the motor tract. With this method, it is possible to monitor the motor function without interfering with the surgical team or with the surgical treatment of infratentorial and spinal lesions. Monitoring of relaxation is necessary to compare the amplitude of MEPs.

Isoflurane plus nitrous oxide versus propofol for recording of motor evoked potentials after high frequency repetitive electrical stimulation

The goal of this study was to test the influence of two widespread techniques of general anesthesia on motor evoked potentials (MEP) in response to transcranial and direct cortical high frequency repetitive electrical stimulation. Total intravenous anesthesia (TIVA) based on propofol and alfentanil was examined in 17 patients (group A), and balanced anesthesia (BA), based on nitrous oxide, isoflurane and fentanyl, was studied in 13 patients (group B). Distinct motor responses were available in 15 of 17 patients (88%) of group A, and in one of 13 patients (8%) of group B. Amplitudes increased significantly with increasing stimulus intensity and number of pulses under conditions of TIVA. At the same time, latencies decreased significantly with increasing stimulus intensity and decreasing interstimulus interval, but not with increasing number of pulses. It is hypothesized that propofol suppresses corticospinal I-waves at the cortical level, resulting in a conduction block at the level of the alpha-motoneuron, and that this effect may be overcome by high frequency repetitive stimulation. In contrast, nitrous oxide and isoflurane seem to have an additional suppressive effect on corticospinal D-waves, which may be overcome by higher stimulation intensity. In conclusion, transcranial high frequency repetitive stimulation and TIVA provide a feasible setting for intraoperative MEP monitoring, while higher doses of nitrous oxide and isoflurane are not compatible with recording of muscular activity elicited by the stimulation technique as described.

Temperament and character personality profiles and personality disorders in chronic pain patients

Abstract In his psychobiological model of personality, Cloninger developed a novel approach concerning the relationships between psychopathological syndromes and personality. We investigated 207 chronic pain patients (CPPs) and compared them to 105 pain‐free control subjects. Participants were assessed using the Temperament and Character Inventory (TCI), the Structured‐Clinical‐Interview‐II, the Beck Depression Inventory and the Spielberger Anxiety Inventory. The CPPs scored higher on the depression and state anxiety scales and 41% fulfilled the criteria of having at least one personality disorder (PD). We used a covariance analysis to control for depression and state anxiety and found that the CPPs scored higher on the Harm Avoidance Temperament Dimension and lower on the Self‐Directedness and Cooperativeness Character Dimensions. In CPPs, the symptom counts of all PD subtypes were significantly related to low Self‐Directedness and, to a lesser degree, low Cooperativeness. The PD symptoms in Cluster A were related to low Reward Dependence, those in Cluster B were related to high Novelty Seeking and the PD symptoms in Cluster C were related to high Harm Avoidance. In multiple hierarchical regression analyses, controlling for age, gender, depression and state anxiety, TCI scales predicted on average 23% in PD symptom counts. The Self‐Directedness and Cooperativeness personality traits appeared to be significant predictors in determining the presence or absence of a PD by correctly classifying 75.8% of CPPs. The TCI provides further insight into the mechanisms underlying the development of chronic pain. This useful diagnostic instrument helps to economically and validly facilitate the identification of core PD features.

Effects of Four Intravenous Anesthetic Agents on Motor Evoked Potentials Elicited by Magnetic Transcranial Stimulation

Transcranial motor cortex stimulation is now being used increasingly to examine patients with motor pathways affection. Two methods of transcranial stimulation are available [5]. Transcranial magnetic stimulation is newer than electric stimulation. For this reason, there is less information available on the intraoperative use and the influence of anesthetics of magnetic stimulation [1, 3, 4, 6, 9, 10]. The aim of this study was to investigate the influence of four different intravenous anesthetics on magnetically evoked compound muscle action potential (magnetic MEP) in humans. Before intraoperative monitoring with magnetic MEP is attempted, compatibility of this modality with anesthetic agents must be established.

Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain

Background and objectives:  Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged‐release (PR) oxycodone when co‐administered with oral naloxone PR.

Gastrointestinal symptoms under opioid therapy: A prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine

Introduction: The purpose of this trial was to evaluate the effect of long‐term treatment with oral sustained‐release hydromorphone, transdermal fentanyl, and transdermal buprenorphine on nausea, emesis and constipation.

Localization of the Epileptic Focus During Methohexital‐Induced Anesthesia

Summary: A short anesthesia was provided by methohexital for painless percutaneous removal of subdural electrodes in 27 patients with medically intractable, complex partial seizures who had undergone invasive preoperative evaluation. Electrocorticographic(ECoG) recordings performed before and during the narcosis were submitted to visual (n = 27) and computerized (n = 3) analysis to obtain additional information about the location of the epileptic focus (or foci). The following observations were made: focal epileptiform potentials were induced in 24 of 27 patients (89%); (b) in 20 of these 24, the induced spikes appeared amid or were followed by isoelectric or subdelta activity. These spikes were characterized by high amplitude as well as rhythmic and synchronized appearance over a circumscribed focal area (or areas) known to be spontaneously epileptogenic. This phenomenon, termed spike‐burst‐suppression (SBS) pattern, allowed identification of the primary epileptic focus in many patients with temporal lobe epilepsy. Further‐more, it indicated a good outcome of epilepsy surgery. Computerized analysis of the induced synchronized spikes (n = 3) allowed further delineation of the primary site of epileptogenicity and quantitative comparison of multiple epileptic generators. ECoG recording during deep methohexital‐induced narcosis is a valuable tool for lateralization and delineation of the primary epileptogenic focus.

Individual value of brain tissue oxygen pressure, microvascular oxygen saturation, cytochrome redox level, and energy metabolites in detecting critically reduced cerebral energy state during acute changes in global cerebral perfusion.

The authors assessed the diagnostic value of brain tissue oxygen tension (PbrO2), microvascular oxygen saturation (SmvO2), cytochrome oxidase redox level (Cyt a+a3 oxidation), and cerebral energy metabolite concentrations in detecting acute critical impairment of cerebral energy homeostasis. Each single parameter as well as derived multimodal indices (arteriovenous difference in oxygen content [AVDO2], cerebral metabolic rate for oxygen [CMRO2], fractional microvascular oxygen extraction [OEF]) were investigated during controlled variation of global cerebral perfusion using a cisternal infusion technique in 16 rabbits. The objective of this study was to determine whether acute changes between normal, moderately, and critically reduced cerebral perfusion as well as frank ischemia defined by local cortical blood flow (lcoBF), brain electrical activity (BEA), and brain stem vasomotor control can be reliably identified by SmvO2, PbrO2, Cyt a+a3 oxidation, or energy metabolites (glutamate, lactate/pyruvate ratio). PbrO2, SmvO2, and Cyt a+a3 oxidation, but not cerebral perfusion pressure, were closely linked to lcoBF and BEA and allowed discrimination between normal, moderately reduced, and critically reduced cerebral perfusion (P < 0.01). Glutamate concentrations and the lactate/pyruvate ratio varied significantly only between moderately reduced cerebral perfusion and frank ischemia (complete loss of BEA and brain stem vasomotor control). Therefore, PbrO2, SmvO2, and Cyt a+a3 oxidation, but not glutamate and the lactate/pyruvate ratio, reliably predict the transition from moderately to critically reduced cerebral perfusion with impending energy failure.

Laxative management in ambulatory cancer patients on opioid therapy: a prospective, open-label investigation of polyethylene glycol, sodium picosulphate and lactulose

Constipation and the laxatives polyethylene glycol (PEG), sodium picosulphate (SPS) and lactulose (L) were investigated in outpatients with cancer and on opioid therapy. Randomly selected patients were enrolled in a prospective, controlled, open-label trial. Endpoints were number of patients taking laxatives >28 days, number of patients with a stool-free interval >72 h (sfi72), dosage, numerical rating scale (NRS) for constipation, and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) questionnaire scores. The 348 patients had comparable demographic and medical data. In this ambulatory population, mobility scores remained unaffected. Constipation incidence was 5.7%, with sfi72 42, mean NRS 2.3557 and mean QoL 2.1. A total of 53.2% discontinued their laxative medication. Laxative use correlated with higher opioid usage (morphine-equivalent mg/day: no laxative 98.2, SPS 128.2, PEG 139.9, L 154.5). PEG was the most frequently prescribed laxative (PEG 27.3%, SPS 10.3%, L 9.2%). PEG (sfi72 12.6%, NRS 2.2, QoL 2.1) and SPS (sfi72 11.1%, NRS 2.7, QoL 2.2) proved more effective than L (sfi72 15.5%, NRS 3.8, QoL 2.5). In spite of opioid therapy, the incidence of constipation was low in these ambulatory cancer pain patients at an early disease stage. For prevention of constipation, PEG or SPS is recommended instead of L.