CNS Measures of Pain Responses Pre- and Post-Anesthetic Ketamine in a Patient with Complex Regional Pain Syndrome.

BACKGROUND: Previous reports have indicated that ketamine anesthesia may produce significant improvement if not complete recovery of patients with complex regional pain syndrome (CRPS). AIMS: Here we report on a patient who had CRPS affecting mainly the right side of her body who underwent functional magnetic resonance imaging (fMRI) scans prior to and in the months following apparent successful treatment with anesthetic doses of ketamine. MATERIALS AND METHODS: The patient underwent two imaging sessions: one during her pain state (CRPS+) and 1 month after her ketamine treatment in her pain-free state (CRPS-). Both spontaneous and evoked (brush, cold, and heat) pain scores decreased from 7­9/10 on a visual analog scale prior to the treatment to 0­1 immediately following and for months after the treatment. For each imaging session, the identical mechanical (brush) and thermal (cold and heat) stimuli were applied to the same location (the skin of the dorsum of the right hand). RESULTS: Comparison of CRPS+ vs CRPS- for the three stimuli showed significant changes throughout the cerebral cortex (frontal, parietal, temporal, cingulate, and hippocampus), in subcortical regions such as caudate nucleus, and in the cerebellum. In addition, resting state network analysis showed a reversal of brain network state, and the recovered state paralleled specific default networks in healthy volunteers. DISCUSSION: The observed changes in brain response to evoked stimuli provide a readout for the subjective response. CONCLUSION: Future studies of brain function in these patients may provide novel insight into brain plasticity in response to this treatment for chronic pain.

[Lidocaine patch for therapy of neuropathic and non-neuropathic pain. A clinical case series of 87 patients]. / Lidocain-Pflaster zur Therapie neuropathischer und nichtneuropathischer Schmerzen. Klinische Fallstudie an 87 Patienten.

BACKGROUND: Topical lidocaine patches (LP) reduce pain in postherpetic neuralgia and other forms of focal neuropathy. The aim of this study was to determine clinical predictors of therapeutic success. MATERIAL AND METHODS: The medical histories of 87 patients with neuropathic (NS) and non-neuropathic pain (NNS) who had received LP as an add-on to their established pain medication were retrospectively analyzed. The variables assessed were gender, age, analgesic co-medication, pain localization, adverse effects and presence of dynamic allodynia. The impact of these variables on the clinical pain-relieving effect (scored on a 5-point scale) was investigated. RESULTS: A total of 24 out of 28 patients with manifest allodynia scored the therapy with LP as beneficial, patients without allodynia (n=59, 67.8%) profited significantly less frequently with only 39% (p<0.001). The probability of profiting from LP therapy in the presence of allodynia was found to be about tenfold higher compared to patients without allodynia (odds ratio 9.14). Of the 87 patients investigated 48 were female (55.2%). Allodynia was considerably more frequent in women (39.6%) compared to men (23.1%) but this was insignificant. Of the female patients 62.5% responded to LP treatment, compared to only 43.6% of men. In more than 60% of cases rated as very good pain relief allodynia was manifest and in non-responders only in less than 10%. The variables age, pain localization and analgesic co-medication were not related with the success of therapy. DISCUSSION: Patients with manifest allodynia profited significantly more frequently from LP therapy and were less frequently non-responders. Female patients showed therapeutic success more often together with a higher rate of allodynia. CONCLUSIONS: In the presence of allodynia, in especially of neuropathic origin, LP seems to be an effective and save option for add-on therapy, this being independent from pain localization and age. Gender specific effects however need more systematic investigation.

Monocyte phagocytosis of viable Staphylococcus aureus is impaired by barbiturates, but not by propofol.

BACKGROUND: Barbiturates and propofol are used for deep sedation of patients with elevated intracranial pressure refractory to standard therapeutic regimens. Such patients often suffer from bacterial infections, which are most commonly caused by Staphylococcus aureus. Various interactions of anesthetics with components of the host defense have been documented, but very little is known about the influence on monocytes, which are a first-line defense against bacterial invasion. Therefore, we studied the effects of thiopental, methohexital, and propofol on monocyte phagocytosis using an in vitro whole blood model of viable S. aureus. MATERIALS AND METHODS: Whole blood samples were preincubated with different concentrations of thiopental, methohexital, and propofol. Phagocytosis was stopped at different time points after addition of viable S. aureus. Monocytes then were stained with monoclonal antibodies for flow cytometric analysis of monocyte recruitment (ratio of ingesting monocytes). Furthermore, the fluorescence intensity of ingested bacteria served as semiquantitative measurement of phagocytosis activity. RESULTS: Both barbiturates inhibited monocyte recruitment and phagocytosis activity concentration-dependently, whereas propofol did not affect any of the investigated parameters. At concentrations of 7.6 x10(-3) M thiopental or 1.1 x 10(-3) M methohexital and greater, monocyte recruitment and phagocytosis activity were significantly inhibited. The calculated half-maximum inhibitory concentration (IC50) of thiopental was 8.4 x 10(-3) M for monocyte recruitment and 8.6 x 10(-3) M for phagocytosis activity. The corresponding values for methohexital were 4.1 x 10(-3) M and 1.1 x 10(-3) M, respectively. CONCLUSION: The two barbiturates induce concentration-dependent inhibition of monocyte phagocytosis, whereas propofol is without effect. In combination with previously described effects on granulocyte function, these findings suggest that defense against bacterial infection might be reduced by barbiturates.

[Effects of reduced shear stress on inflammatory reactions in vitro. Effects of pathological flow conditions on leukocyte-endothelial interactions and monocyte tissue factor expression in human cell cultures]. / Einfluss verminderter Scherkräfte auf Entzündungsreaktionen in vitro Effekte pathologischer Strömungsbedingungen auf Leukozyten-Endothel-Interaktionen und monozytäre "Tissue-factor-Expression" in humanen Zellkulturen.

BACKGROUND: During malperfusion and inflammation leukocyte adhesion is common. The purpose of this study was to examine the effects of reduced shear stress on leukocyte-endothelial interactions and subsequent inflammatory reactions such as up-regulation of tissue factor. METHODS: Isolated neutrophils and monocytes were co-incubated with human umbilical venous endothelium at 0-3 dynes/cm(2) in a flow chamber. Adhesion and tissue factor expression on adherent leukocytes were examined at various flow conditions. RESULTS: At 2-3 dynes/cm(2) adhesion occurred only on TNFalpha-activated endothelium. Below 1 dyne/cm(2) similarly increased adhesion was also observed on non-activated endothelium. As was observed for leukocyte adhesion, these shear stress-dependent cell interactions also resulted in an up-regulation of tissue factor on adherent monocytes from non-activated co-cultures. CONCLUSION: Apart from additional activators of inflammation, reduced shear forces may directly contribute to inflammation.

[Aortocaval compression syndrome]. / Aortokavales Kompressionssyndrom.

Aortocaval compression syndrome (supine hypotensive syndrome) represents a common complication mainly of late pregnancy, although the syndrome has been described to occur as early as 16 weeks of gestation. The nature and severity of symptoms range from unspecific complaints to severe maternal hypotension, loss of consciousness, cardiovascular collapse, and consecutive fetal depression. Predominantly, the syndrome is provoked by placing the parturient supine. Since supine positioning is required for diverse diagnostic and therapeutic procedures in obstetrics, these involve increased risk of aortocaval compression. For the anesthetist, cesarean section is most relevant, because of the coincidence of several risk factors. The following article begins by reviewing the pathophysiology of the syndrome, known risk factors and anesthesiological procedures that predispose to the syndrome. The second part is concerned with prophylactic measures and therapeutic options, together with the discussion of a clinically practicable algorithm.

Phantom limb pain: a report of two cases.

The efficacy of pre-emptive analgesia for phantom limb pain is still unclear. It is generally accepted that pre hyphen;amputation pain increases the incidence of phantom and stump pain, even if pre-emptive analgesia is performed before and during surgery and in the postoperative period. Two cases of traumatic upper limb amputations are described here with no pre-existing pain. Both received similar antinociceptive treatment by continuous block of the brachial plexus through infusion of ropivacaine 0.375% at 5 ml/h for 10 days. Treatment of case 1 was initiated immediately after surgery; however, this amputee developed intensive phantom limb pain which persisted at 6 months. Early use of the prosthesis after surgery was not possible for this patient. The intensity of phantom limb pain in case 2 decreased significantly after 6 months, even though brachial plexus blockade was not started until 5 weeks post-trauma. This patient used a functional prosthesis intensively beginning early after amputation. Serial magnetoencephalographic recordings were performed in both patients. Only case 2 showed significant changes of cortical reorganization. In case 1 markedly less cortical plasticity was found. A combination of relevant risk factors such as a painful neuroma, behavioural and cognitive coping strategies and the early functional use of prostheses are discussed as important mechanisms contributing to the development of phantom pain and cortical reorganization.

The efficacy of postoperative incentive spirometry is influenced by the device-specific imposed work of breathing.

STUDY OBJECTIVES: The study evaluated the impact of the additional imposed work of breathing (WBimp) generated by two different spirometers on postoperative incentive spirometry performance in patients at high risk and moderate risk for postoperative pulmonary complications (PPCs). Additionally, we investigated whether maximal inspiratory pressure (PImax) is an easy estimate of the WBimp imposed by incentive spirometers. DESIGN: Prospective, randomized, single-blind clinical trial. SETTING: ICU of a university hospital. INTERVENTIONS AND MEASUREMENTS: Thirty male patients were assigned to a group at high risk for PPCs (group A; inspiratory capacity [IC], < 1.6 L) or to a group at moderate risk for PPCs (group B; IC, 1.6 to 2.5 L) after upper-abdominal, thoracic, or two-cavity surgery. On the first or second postoperative day WBimp, IC, and PImax were recorded without spirometers (baseline) and during incentive spirometry with the Mediflo spirometer (Medimex; Hamburg, Germany) (high WBimp) and the Coach spirometer (Kendall; Neustadt, Germany) (low WBimp) using a pneumotachograph. In group A, the baseline and the ICs for both spirometers only differed slightly. In group B, the IC was significantly reduced for the Mediflo (p < 0.05), which imposed a WBimp twice as high as the Coach (p < 0.01). PImax was significantly increased for both the Mediflo and the Coach (p < 0.01). PImax was positively correlated with WBimp (r = 0.8). CONCLUSIONS: Incentive spirometers differ considerably in their additional Wbimp with a potential impact on the efficacy of postoperative incentive spirometry performance. PImax might be an easy clinical estimate for the WBimp during incentive spirometry. Incentive spirometers with low WBimp permit increased maximal sustained inspiration and, thus, enhanced incentive spirometry performance, and, therefore, it might be more suitable for use in postoperative respiratory care.

Low-dose oral clonidine as premedication before intraocular surgery in retrobulbar anesthesia.

PURPOSE: We investigated whether low-dosed oral clonidine premedication before elective intraocular surgery in retrobulbar anesthesia is effective in terms of anxiolysis, sedation, stable hemodynamics, lower intraocular pressure and perioperative endocrine stress response. METHODS: In a prospective, randomised, double-blind study, 44 patients scheduled for elective intraocular surgery received either 0.15 mg clonidine (n=22) or a matched placebo (n=22) orally 60 minutes before retrobulbar anesthesia. The main study parameters were sedation, anxiolysis, hemodynamics and intraocular pressure. Additionally, mediators of endocrine stress responses were measured five times, in 13 patients after clonidine and 12 after placebo. RESULTS: After clonidine 86% of the patients showed sedation and after placebo 90.9% showed no sedation (p<0.01). Clonidine produced effective anxiolysis (Erlanger-Anxiety-Scale: 31.6 +/- 2.6 points vs. 38.1 +/- 8.5 points) before the operation (p<0.01). Systolic blood pressure was significantly lower after clonidine. Effects on mean and diastolic blood pressure were small but statistically significant. Norepinephrine and cortisol plasma concentrations were significantly lower after clonidine. Intraocular pressure was significantly lower too (p<0.05). No clinically relevant adverse effects were observed e.g. inappropriate sedation, hypotension (<100 mmHg), bradycardia (<50 bpm) or hypoxemia (SpO2<90%). CONCLUSIONS: Oral low-dose clonidine produces light sedation, significant anxiolysis and stable hemodynamics, and attenuates the endocrine response to perioperative stress. Thus, clonidine seems sufficient to increase patient comfort for intraocular surgery and might even offer clinically worthwhile benefits such as stable hemodynamics and a reduced response to perioperative stress.

Cortical reorganization after digit-to-hand replantation.

Functional recovery after digit-to-hand replantation depends on the interaction of various factors. In addition to peripheral mechanisms, cortical and subcortical reorganization of digit representation may play a substantial role in the recovery process. However, cortical processes during the first months after replantation are not well understood. In this 25-year-old man who had traumatically lost digits II to V (DII-V) on his right hand, the authors used magnetoencephalographic source imaging to document the recovery of somatosensory cortical responses after tactile stimulation at four sites on the replanted digits. Successful replantation of DIV and DV was accomplished at the original position of DIII and DIV with mixed innervation. Cortical evoked fields could be recorded starting from the 10th week after digit-to-hand replantation. Initially, signals from all sites showed decreased amplitudes and prolonged latencies. In the subsequent six recordings obtained between the 12th and 55th week postreplantation, a continuous increase in amplitude but only a slight recovery of latencies were observed. Components of the recorded somatosensory evoked fields were localized in the primary somatosensory cortex (SI). The localizations of the replanted DIV showed a gradual lateral-inferior shift in the somatosensory cortex over time, indicating cortical reorganization caused by altered peripheral input. The authors infer from this shift that the original cortical area of the missing finger (DII) was taken over by the replanted finger. From these data the authors conclude that magnetic source imaging might be a reliable noninvasive method to evaluate surgical nerve repair and that cortical reorganization of SI is involved in the regeneration process following peripheral nerve injury.

The endocrine stress response after oral premedication with low-dose midazolam for intraocular surgery in retrobulbar anaesthesia.

PURPOSE: It was the purpose of this study to examine the endocrine stess response in patients undergoing elective intraocular surgery in retrobulbar anaesthesia (RBA), and the effect of an oral premedication with 3.75 mg midazolam on this reaction. METHODS: In a prospective double-blind study, 23 patients were randomly assigned to either group I (n = 12), receiving 3.75 mg midazolam, or group II (n = 11), receiving a matched placebo 60 min before RBA. Plasma concentrations of known mediators of the endocrinological stress response were analysed at five perioperative times: adrenocorticotropic hormone (ACTH), cortisole (CORT), somatotropic hormone (STH), epinephrine (EPI), norepinephrine (NOR), and dopamine (DOP). RESULTS: The observed endocrinological reaction was moderate. Perioperative anxiety and, above all, RBA were the main stressors. The endocrine stress response could best be seen within the fast-reacting sympathoadrenergic system. Midazolam significantly suppressed the epinephrine and the cortisole answer (p < 0.01). After RBA an ACTH plasma peak only was observed after placebo. Plasma-STH showed extreme variability. An STH-peak after midazolam is presumably due to a gonadotropic hormone-releasing hormone (GHRH) secretion directly stimulated by midazolam. Midazolam had no significant effect upon norepinephrine. A significant (p < 0.01) increase for plasma-cortisole was seen 60 min after the operation when compared to preoperative values. CONCLUSIONS: The results indicate that even at a low dose midazolam positively influences the endocrine stress response. The combination of this stress-reducing effect with the well-known hemodynamic stability, the distinct anxiolytic and sedative action, suggest low-dose midazolam as a favourable premedication for intraocular surgery.

Oral low-dose midazolam as premedication for intraocular surgery in retrobulbar anesthesia: cardiovascular effects and relief of perioperative anxiety.

The aim was to investigate the efficacy and practicability of oral low-dose premedication with 3.75 mg midazolam (1/2 tablet Dormicum 7.5 mg) for selective intraocular surgery with retrobulbar anesthesia. Forty-six ASA II-III patients were randomly assigned to either group I: midazolam (n = 24) or group II: placebo (n = 22). Sedation was objectively quantified with a scale derived from the Glasgow-Coma-Scale and a verbal self-rating scale. Trait-anxiety was studied with the State-Trait Inventory by Spielberger, perioperative situative anxiety with the Erlanger Anxiety Scale. Cardiovascular variables and oxygenation were automatically monitored. Midazolam produced significant and sufficient sedation and significant anxiolysis. Systolic, diastolic and mean blood pressure were moderately but significantly, reduced. The effect on diastolic pressure was more pronounced. There was no effect on heart-rate. Oxygenation at all times remained well above 90% SpO2. In conclusion low-dose oral midazolam proved to be a single and effective premedication before intraocular surgery under local anesthesia.