Abstract: Pulsed radiofrequency treatment has been described as a nonablative alternative to radiofrequency thermocoagulation for the management of certain chronic pain syndromes. We present our first three patients with long-standing cluster headaches who were treated with pulsed radiofrequency to the sphenopalatine ganglion. All three patients have had cluster headaches for more than 10 years' duration and experienced minimal relief with conservative treatment. An excellent midterm effect was achieved in two of the three patients and a partial effect in one. No neurological side effects or complications were reported. Quantitative sensory testing consisting of allodynia testing, pressure-pain thresholds, electrical pain thresholds, and conditioned pain modulation (CPM) response testing were used to monitor their sensory processing changes before and after the procedure. From this case series, it might be that cluster headache patients with an impaired CPM response with or without signs of allodynia will respond less favorably to interventional treatment. Further studies are required to validate this hypothesis.
Abstract: Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution of EEG rhythmicity in patients with CP.
Abstract: Physical complaints, such as pain, can be effectively reduced by placebo effects through induction of positive expectations, or increased by nocebo effects through induction of negative expectations. In the present study, verbally induced nocebo and placebo effects on itch were experimentally investigated for the first time. In part 1, the role of verbal suggestions in inducing nocebo effects on itch and pain was investigated. All subjects received the same somatosensory quantitative sensory testing stimuli, that is, mechanical and electrical stimuli and application of histamine, and verbal suggestions to manipulate expectations regarding the stimuli. The suggestions were designed to produce either high expectations for itch (itch nocebo) or pain (pain nocebo) or low expectations for itch (itch nocebo control) or pain (pain nocebo control). Results showed that high itch and pain expectations resulted in higher levels of itch and pain, respectively. When comparing nocebo effects, induced by verbal suggestions, results were more pronounced for itch than for pain. In part 2, verbal suggestions designed to produce a placebo effect on itch (itch placebo) or pain (pain placebo), or neutral suggestions (itch placebo control and pain placebo control) were given regarding a second application of histamine and compared with the first application applied in part 1. Results of placebo effects only showed a significantly larger decrease in itch in the itch placebo condition than in the pain placebo condition. In conclusion, we showed for the first time that nocebo and possibly placebo responses can be induced on itch by verbal suggestions. Experiments of nocebo and placebo effects on itch and pain demonstrated that particularly nocebo effects can be induced on itch and pain by verbal suggestions.
Abstract: BACKGROUND & AIMS: Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain disorders. We investigated whether agents used to treat patients with neuropathic pain are effective in CP. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the effects of the gabapentoid pregabalin as an adjuvant analgesic. We measured pain relief, health status, quality of life, and tolerability in 64 patients with pain from CP; they were randomly assigned to groups given increasing doses of pregabalin or placebo (control) for 3 consecutive weeks. The primary end point was pain relief, based on a visual analog scale documented by a pain diary. Secondary end points included Patients' Global Impression of Change (PGIC) score, changes in physical and functional scales, pain character, quality of life, and tolerability. RESULTS: Pregabalin, compared with placebo, caused more effective pain relief after 3 weeks of treatment (36% vs 24%; mean difference, 12%; 95% confidence interval, 22%-2%; P = .02). The incidence of patients with much or very much improved health status (PGIC score) at the end of the study was higher in the pregabalin than the control group (44% vs 21%; P = .048). Changes in physical and functional scales, pain character, quality of life, and number of serious adverse events were comparable between groups. CONCLUSIONS: In a placebo-controlled trial, pregabalin is an effective adjuvant therapy for pain in patients with CP.
Abstract: Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive N-methyl-d-aspartate antagonist, in modulating generalized hyperalgesia in chronic pancreatitis pain.
Abstract: Long-term potentiation (LTP) in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.
Abstract: ABSTRACT Chronic pain is increasingly recognized as an undesirable outcome after surgery. Predicting risk of postoperative chronic pain, as well as chronic pain prevention or treatment, requires understanding of the processes underlying its development. Quantitative sensory testing research over the last decade has made it possible to start understanding the alterations in central pain processing associated with chronic pain and its development. Chronic pain syndromes are typically characterized by a pronociceptive state of pain processing, e.g., generalized hyperalgesia as a sign of supraspinal central sensitization and poor inhibitory or even facilitatory descending modulation. In the perioperative context, development and progression of chronic pain are accompanied by signs congruent with a shift towards a pronociceptive state. Preoperatively, hyperalgesia and poor descending inhibitory modulation appear to increase the risk of subsequent chronic pain. Postoperatively, abnormal persistence and spread of hyperalgesia, compatible with rostral neuraxial spread of central sensitization, are increasingly linked to the development and progression of chronic pain. These findings, which need further confirmation, suggest that perioperative quantitative sensory testing of pain sensitivity and pain modulation has the potential to become a valuable clinical tool for assessing risk of chronic pain development and for managing its prevention and treatment.
Abstract: : Diagnostic blocks of cervical zygapophysial joints have been used as part of the management strategy for patients with chronic neck pain. Little information is available regarding the sensory processing changes that occur after these common procedures. In a hypothesis-generating prospective study, the pressure-pain thresholds, electrical pain thresholds, and descending inhibitory modulation response using the conditioned pain modulation paradigm are described for 9 patients with cervical zygapophysial joint pain that underwent successful comparative diagnostic blocks.
Abstract: Objective In patients with painful chronic pancreatitis (CP) there is increasing evidence of abnormal pain processing in the central nervous system. Using magnetic resonance (MR) diffusion tensor imaging, brain microstructure in areas involved in processing of visceral pain was characterised and these findings were correlated to clinical pain scores. Methods 23 patients with CP pain and 14 controls were studied in a 3T MR scanner. Apparent diffusion coefficient (ADC) (ie, diffusivity of water) and fractional anisotropy (FA) (ie, organisation of fibres) values were assessed in the amygdala, cingulate cortex, insula, prefrontal cortex and secondary sensory cortex. Daily pain scores and the Brief Pain Inventory Short Form were collected 1 week before the investigation. Results In grey matter, patients had increased ADC values in amygdala, cingulate cortex, insula and prefrontal cortex, as well as decreased FA values in cingulate cortex and secondary sensory cortex. In white matter, patients had increased ADC values in insula and prefrontal cortex, and decreased FA values in insula and prefrontal cortex (all p values <0.05). An effect modification from the pain pattern (attacks vs continuous pain) was seen in the insula and secondary sensory cortex (p values <0.05), but no effect modifications from diabetes, alcoholic aetiology and opioid treatment were seen (all p values >0.05). Microstructural changes in cingulate and prefrontal cortices were correlated to patients' clinical pain scores. Conclusion The findings suggest that microstructural changes of the brain accompany pain in CP. The changes are likely to be a consequence of ongoing pain and structural reorganisation of the neuromatrix as also seen in other diseases characterised by chronic pain.
Abstract: Background: It is not known why some patients with underlying chronic nociceptive sources in the neck develop cervicogenic headache (CEH) and why others do not. This quantitative sensory testing (QST) study systematically explores the differences in sensory pain processing in 17 CEH patients with underlying chronic cervical zygapophysial joint pain compared to 10 patients with chronic cervical zygapophysial joint pain but without CEH. Methods: The QST protocol comprises pressure pain threshold testing, thermal detection threshold testing, electrical pain threshold testing and measurement of descending inhibitory modulation using the conditioned pain modulation (CPM) paradigm. Results: The main difference between patients with or without CEH was the lateralization of pressure hyperalgesia to the painful side of the head of CEH patients, accompanied by cold as well as warm relative hyperesthesia on the painful side of the head and neck. Discussion: From this hypothesis-generating study, our results suggest that rostral neuraxial spread of central sensitization, probably to the trigeminal spinal nucleus, plays a major role in the development of CEH.
Abstract: Long-term potentiation (LTP) is a cellular model of synaptic plasticity and reflects an increase of synaptic strength. LTP is also present in the nociceptive system and is believed to be one of the key mechanisms involved in the manifestations of chronic pain. LTP manifested as an increased response in pain perception can be induced in humans using high-frequency electrical stimulation (HFS). The aim of this study was to induce spinal heterosynaptic LTP using HFS and investigate its heterotopic effects on event-related potentials (ERPs) to repeated nonpainful cutaneous stimuli as a possible electrophysiological cortical correlate of sensitization. Twenty-two healthy subjects were randomly assigned to one of the two experimental conditions: HFS and control stimulation. Before and after the stimulation, both conditions received heterotopic mechanical (pinprick) and paired nonpainful electrical test stimuli to quantify and confirm the effects of HFS on the behavioral level. ERPs to paired nonpainful electrical stimulation were measured simultaneously. Conditioning HFS resulted in significant heterotopic effects after 30 min, including increased perceived intensity in response to (pinprick) mechanical and paired nonpainful electrical stimulation compared with control. The paired nonpainful electrical stimuli were accompanied by significantly enhanced responses regarding the ERP N1-P2 peak-to-peak and P300 amplitude compared with control. These findings suggest that HFS is capable of producing heterosynaptic spinal LTP that can be measured not only behaviorally but also using ERPs.
Abstract: Patients frequently report high levels of physical symptoms, such as itch and pain, which do not completely correspond to pathophysiological findings, possibly indication heightened sensitivity to physical symptoms. Sensitivity to itch and pain is thought to be affected by processes such as attentional focus on bodily sensations. We investigated the role of attentional focus in sensitivity to various somatosensory stimuli evoking both itch and pain sensations in healthy female subjects. Different mechanical, chemical and electrical stimuli of quantitative sensory testing were applied. Attentional focus on bodily sensations was measured using validated questionnaires. The results indicated that focusing on bodily sensations is associated with higher levels of experienced itch and pain but not with tolerance to stimuli. This suggests that attentional focusing on bodily sensations is a mechanism responsible for sensitivity to different physical sensations, such as itch and pain.
Abstract: Pain can be endogenously modulated by heterotopic noxious conditioning stimulation (HNCS) through a mechanism which is known as diffuse noxious inhibitory control (DNIC). Since DNIC can be impaired in patients suffering from chronic pain, a comparable impaired itch inhibition may exist in patients suffering from chronic itch. The aim of the present study was to investigate whether heterotopic pruritic conditioning stimulation (HPCS) would display an impaired modulation of itch in patients suffering from chronic itch compared with healthy subjects. To this end, electrical stimuli were applied before and after histamine application (HPCS) to female patients with psoriasis and healthy female control subjects. Subjects reported the intensity of electrically evoked itch before and after HPCS. In order to replicate earlier findings for DNIC, electrically evoked pain was additionally investigated before and after cold stimulation (HNCS). As expected, the intensity of itch evoked by the electrical stimulus was significantly less after than before HPCS in healthy subjects, and the same was found for the intensity of electrically evoked pain after compared to before HNCS. Contrarily, in the patients levels of electrically evoked itch were significantly higher after than before HPCS, and no significant difference in pain intensity before and after HNCS was observed. In line with pain modulation, results suggest that there is a DNIC analogous mechanism for itch, i.e., diffuse pruritic inhibitory control (DPIC), which is impaired in patients with chronic itch, possibly due to a dysregulation of descending itch modulatory systems.
Abstract: Pain treatment in chronic pancreatitis patients is difficult, with pain frequently relapsing or persisting. Recent studies suggest that altered central nervous system pain processing underlies the chronic pain state in these patients. There is evidence that increased sympathetic activity may also play a role in some chronic pain syndromes. This study assessed sympathetic nervous system activity and its relation to pain processing in patients with severe painful chronic pancreatitis. The authors postulated that chronic pancreatitis patients with more sympathetic activity exhibit more generalized hyperalgesia. In 16 chronic pancreatitis patients, sympathetic activity was measured via venous plasma norepinephrine (NE) levels (supine, standing). Pain processing was quantified via pressure pain tolerance thresholds (PPTs) in dermatomes T10 (pancreatic area), C5, T4, L1. Five patients showed increased supine plasma NE levels (NE ≥ 3.0 nmol/L). PPTs were lower in patients with increased NE levels (INE) compared with patients with normal NE (NNE) (means [95% confidence interval]: INE 402 kPa [286-517] versus NNE 522 kPa [444-600]; P = .042). In severe chronic pancreatitis patients, increased sympathetic activity and hyperalgesia appear associated, suggesting that sympathetic activity may also play a role in these patients' pain.
Abstract: Chronic pain is common and undesirable after surgery. Progression from acute to chronic pain involves altered pain processing. The authors studied relationships between presence of chronic pain versus preoperative descending pain control (diffuse noxious inhibitory controls; DNICs) and postoperative persistence and spread of skin and deep tissue hyperalgesia (change in electric/pressure pain tolerance thresholds; ePTT/pPTT) up to 6 months postoperatively. In 20 patients undergoing elective major abdominal surgery under standardized anesthesia, we determined ePTT/pPTT (close to [abdomen] and distant from [leg] incision), eDNIC/pDNIC (change in ePTT/pPTT with cold pressor pain task; only preoperatively), and a 100 mm long pain visual analogue scale (VAS) (0 mm = no pain, 100 mm = worst pain imaginable), both at rest and on movement preoperatively, and 1 day and 1, 3, and 6 months postoperatively. Patients reporting chronic pain 6 months postoperatively had more abdominal and leg skin hyperalgesia over the postoperative period. More inhibitory preoperative eDNIC was associated with less late postoperative pain, without affecting skin hyperalgesia. More inhibitory pDNIC was linked to less postoperative leg deep tissue hyperalgesia, without affecting pain VAS. This pilot study for the first time links chronic pain after surgery, poorer preoperative inhibitory pain modulation (DNIC), and greater postoperative degree, persistence, and spread of hyperalgesia. If confirmed, these results support the potential clinical utility of perioperative pain processing testing.
Abstract: Pain is a prominent symptom in chronic pancreatitis (CP), but the underlying mechanisms are incompletely understood. We investigated the role of descending pain modulation from supraspinal structures as well as central nervous system sensitization in patients with pain from CP.
Abstract: The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to clinicians about the underlying symptoms and treatment of these patients.
Abstract: Physiotherapy is considered an important treatment option in patients with upper limb complex regional pain syndrome type-1 (CRPS-1). In case of chronic CRPS-1, exercise therapy of the affected limb forms an important part of the physiotherapeutic program. We investigated whether muscle loading in chronic CRPS-1 patients is associated with impairments in muscle circulation of the forearm of the affected limb.
Abstract: Interscalene brachial plexus block is associated with 100% incidence of hemidiaphragmatic paresis as a result of phrenic nerve block. We examined whether an ultrasound (US)-guided interscalene brachial plexus block performed at the level of root C7 versus a nerve stimulation interscalene brachial plexus block, both using 10 mL of ropivacaine 0.75%, resulted in a lower incidence of hemidiaphragmatic paresis.
Abstract: Transcutaneous electrical nerve stimulation (TENS) is an easy to use non-invasive analgesic intervention applied for diverse pain states. However, effects in man are still inconclusive, especially for chronic pain. Therefore, to explore the factors predicting result of TENS treatment in chronic pain we conducted a prospective, randomized, placebo-controlled trial (n=163), comparing high frequency TENS (n=81) with sham TENS (n=82). Patients' satisfaction (willingness to continue treatment; yes or no) and pain intensity (VAS) were used as outcome measures. The origin of pain and cognitive coping strategies were evaluated as possible predictors for result of TENS treatment. Results: Fifty-eight percent of the patients in the TENS group and 42.7% of the sham-TENS group were satisfied with treatment result (chi square=3.8, p=0.05). No differences were found for pain intensity. Patients diagnosed with osteoarthritis and related disorders (especially of the vertebral column) or peripheral neuropathic pain were less satisfied with high frequency TENS (OR=0.12 (95% CI 0.04-0.43) and 0.06 (95% CI 0.006-0.67), respectively). Injury of bone and soft tissue (especially postsurgical pain disorder) provided the best results. Treatment modality or interactions with treatment modality did not predict intensity of pain as a result of treatment. We conclude, that predicting the effect of high frequency TENS in chronic pain depends on the choice of outcome measure. Predicting patients' satisfaction with treatment result is related to the origin of pain. Predicting pain intensity reflects mechanisms of pain behavior and perceived control of pain, independent of treatment modality. Pain catastrophizing did not predict TENS treatment outcome.
Abstract: Bilateral thoracoscopic splanchnicectomy is a minimally invasive method of treating pain in patients with chronic pancreatitis. It offers good, short-term pain relief, but long-term success is difficult to predict. We analyze long-term results and identify factors predicting success of splanchnicectomy.
Abstract: Chronic pain after breast cancer surgery is a major problem and is expected to increase in the coming years because of an increased prevalence of breast cancer coupled with better survival. Axillary lymph node dissection (ALND) in patients with breast cancer is associated with nerve damage. The present study investigated the effect of ALND on the prevalence and intensity of chronic pain after breast cancer surgery. Furthermore, we studied the effect of chemotherapy and radiotherapy on chronic pain and the quality of life after breast cancer surgery. We analyzed 317 questionnaires of patients who underwent surgery for breast cancer between 2002 and 2004. In the first part, questions were asked concerning the prevalence of chronic pain, its intensity (visual analog scale), and phantom breast pain. The second part covered quality of life and included the EORTC QLQ-C30/BR-23. The prevalence of chronic pain after breast cancer surgery with ALND is double that without ALND (51% vs 23%). Chronic pain intensity and prevalence of phantom breast pain were not influenced by ALND. Chemotherapy and radiotherapy in interaction with ALND were associated with increased prevalence of chronic pain. The quality of life in patients was mainly affected by chronic pain and to a lesser extent by type of surgery. PERSPECTIVE: Nerve injury is particularly efficient at producing central sensitization. ALND in conjunction with breast cancer surgery is associated with a doubled prevalence of chronic pain, which has not been described to date. ALND and nerve injury may play a major role in pain chronification after breast cancer surgery.
Abstract: Chronic pain is a common complication after thoracic surgery. The cause of chronic post-thoracotomy pain is often suggested to be intercostal nerve damage. Thus chronic pain after thoracic surgery should have an important neuropathic component. The present study investigated the prevalence of the neuropathic component in chronic pain after thoracic surgery. Furthermore, we looked for predictive factors for prevalence and intensity of chronic pain. We contacted 243 patients who underwent a video-assisted thoracoscopy (VATS) or thoracotomy in the period between January 2004 and September 2006 by mail. Patients retrospectively received a questionnaire with the Dutch version of the PainDETECT Questionnaire, a validated screening tool for neuropathic pain. Results were analyzed from 204 patients (144 thoracotomies, 60 VATS). The prevalence of chronic pain was 40% after thoracotomy and 47% after VATS. Definite chronic neuropathic pain was present in 23% of the patients with chronic pain, with an additional 30% having probable neuropathic pain. Greater probability of neuropathic pain (ie, a higher total score of the PainDETECT) correlated with more intense chronic pain. Predictive factors for chronic pain were younger age (P = .01), radiotherapy (P = .043), pleurectomy (P = .04) and more extensive surgery (P < .001). PERSPECTIVE: Up to half the chronic pain after thoracic surgery is not associated with a neuropathic component, which has not been reported to date. More extensive surgery and pleurectomy are predictive factors for chronic pain after thoracic surgery, suggesting a visceral component apart from nerve injury.
Abstract: Central sensitisation due to visceral pancreatic nociceptive input may play an important role in chronic pancreatitis pain. Using quantitative sensory testing (QST), this first study investigates whether thoracoscopic splanchnic denervation (TSD), performed to reduce nociceptive visceral input, affects central sensitisation in chronic pancreatitis patients.
Abstract: Physicians are frequently confronted with patients reporting severe itch and pain. Particularly in patients suffering from persistent itch and pain, central and peripheral sensitization processes are assumed to be involved in the long-term maintenance and aggravation of the symptoms. The present study explores generalized and symptom-specific sensitization processes in patients suffering from persistent itch and pain. Specifically, it examines whether patients with chronic itch and pain are more sensitive to somatosensory stimuli (generalized sensitization) and simultaneously perceive somatosensory stimuli as a symptom of their main physical complaint, e.g. pain in chronic pain patients (symptom-specific sensitization).
Abstract: Dysmenorrhoea patients experience intense visceral pain during menstruation. Recurrent and/or intense visceral pain can induce facilitation of somatic and visceral nociceptive processing which can lead to viscero-somatic (referred) and viscero-visceral hyperalgesia. Our aim was to study if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. We measured skin sensitivity in the referred area of the sigmoid colon as well as stimulus-response relationships in the sigmoid colon and rectum. The latter were measured using mechanical (balloon) distension applied via a Barostat in 11 dysmenorrhoea patients without gastro-intestinal complaints and 10 healthy and age matched women, again without gastrointestinal complaints. We found no skin hypersensitivity in the colonic referred area. In contrast, significantly lower distension volumes were seen at each threshold in dysmenorrhoea patients, particularly in the sigmoid colon. The mean reduction in colonic distension volume thresholds for dysmenorrhoea patients vs. controls was 57% at the detection threshold and 39% at the pain threshold. There were no differences in compliance between the groups. These findings suggest that, despite the absence of overt gastro-intestinal symptoms or viscero-somatic sensitisation, dysmenorrhoea patients demonstrate intestinal hypersensitivity. This can be regarded as the result of centrally mediated viscero-visceral hyperalgesia due to recurrent intense menstrual pain.
Abstract: Visceral nociception readily sensitizes the central nervous system, causing referred somatic pain and hyperalgesia via somato-visceral convergence. Hyperalgesia in the perioperative period may increase vulnerability to subsequent development of chronic pain. The study aim is to investigate the role of angina pectoris, an ischemic visceral pain, in long-term pain after coronary artery bypass surgery (CABG). We sent questionnaires to 369 patients who underwent CABG surgery in 2003. Questions were asked about angina pectoris and other pain in the period before surgery, the first week postoperatively (= acute pain), and the period after 3 months after surgery (= chronic pain). We obtained results from 256 patients (response rate = 69%). The point prevalence of chronic pain after CABG was 27% after a mean follow-up of 16 months (SD +/- 3 months). Patients with chronic pain after CABG had more angina pectoris than those without chronic pain: Before surgery (P = .07), early on postoperatively (P = .004), and more than 3 months after surgery (P = .000004). We found cumulative prevalences of chronic pain after CABG at 3 months of 39%, and of 32% after 6 months. Other predictive factors for chronic pain after CABG were acute postoperative pain (P = .00002) and younger age (P = .002). Angina pectoris is associated with chronic pain after CABG surgery. Other predictive factors include acute postoperative pain and younger age. PERSPECTIVE: The influence of postoperative angina pectoris for chronic pain after CABG surgery has not been described in the literature to date. Visceral nociception may play an important role in the development of chronic pain after surgery and should be taken into account in future studies.
Abstract: The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (L4).
Abstract: The pain of chronic pancreatitis remains challenging to manage, with treatment all too often being unsuccessful. A main reason for this is lacking understanding of underlying mechanisms of chronic pain in these patients.
Abstract: Complex Regional Pain Syndrome type 1 (CRPS 1) is a potentially incapacitating complication in which pain seems to be the most disabling factor. We performed a late follow up study of a well-defined CRPS 1 population more than eight years after diagnosis. The relationships between early and late impairments were studied with a view to outcome prediction and to investigate possible differences in long-term impairments according to initial CRPS 1 subdiagnosis (i.e. "warm" or "cold", diagnosed according to skin temperature measured via infrared thermometer).
Abstract: Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.
Abstract: The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients' satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.
Abstract: In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks.
Abstract: Chronic pain is common after thoracotomy. The primary goal of this study was to investigate the incidence of chronic post-thoracotomy pain. The secondary goal was to identify possible risk factors associated with the development of chronic post-operative pain.
Abstract: Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in the elderly population. A major challenge for the physician prescribing opioids in the elderly is their greater risk of medication-associated problems. Thus, older patients suffer increased vulnerability to adverse drug effects and interactions, higher rates of polypharmacy, and more comorbidity. These problems are compounded by a relative lack of definitive published information. There is clearly a need for more research in this area. Aging affects opioid pharmacokinetics via altered body composition (distribution volumes) and organ function (liver=metabolism, kidney=excretion). Pharmacodynamics is affected via impaired neurotransmitter/peptide production and changed receptor affinities/populations. Older women may need less morphine analgesia postoperatively, while pain sensitivity tends to increase particularly in older men. However, the net effects of changes in opioid pharmacology with age on clinical opioid analgesia remain unclear, probably due to the significantly greater variability in body function with increasing age. Practical recommendations for opioid prescription in the elderly include meticulous review of indication for opioid use, not only initially but also at regular intervals thereafter. A policy of careful titration should be followed, with conservative choice of dosage on starting. Dosing intervals may need to be lengthened subsequently. Finally, it should be remembered that old persons do not necessarily need less opioid than younger ones.
Abstract: We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.
Abstract: Selective segmental nerve blocks with local anesthetics are applied for diagnostic purposes in patients with chronic back pain to determine the segmental level of the pain. We performed this study to establish myotomal motor effects after L4 spinal nerve blocks by lidocaine and ropivacaine and to evaluate the relationship with pain. Therefore, 20 patients, of which 19 finished the complete protocol, with chronic lumbosacral radicular pain without neurological deficits underwent segmental nerve blocks at L4 with both lidocaine and ropivacaine. Pain intensity scores (verbal numeric rating scale; VNRS) and the maximum voluntary muscle force (MVMF; using a dynamometer expressed in newtons) of the tibialis anterior and quadriceps femoris muscles were measured on the painful side and on the control side. The median VNRS decrease was 4.0 (P < 0.00001; Wilcoxon's signed rank test), without significant differences between ropivacaine and lidocaine (Mann-Whitney U-test). A difference in effect on MVMF was found for affected versus control side (P = 0.016; Tukey test). Multiple regression revealed a significant negative correlation for change in VNRS score versus change in median MVMF (Spearman R = -0.48: P = 0.00001). This study demonstrates that in patients with unilateral chronic low back pain radiating to the leg, pain reduction induced by local anesthetic segmental nerve (L4) block is associated with increased quadriceps femoris and tibialis anterior MVMF, without differences for lidocaine and ropivacaine.
Abstract: Altered central nervous system sensory processing (neuroplasticity) is a basic mechanism underlying postoperative pain that can be made visible using quantitative sensory testing. Using quantitative sensory testing, the authors investigated how perioperative analgesia affects postoperative neuroplasticity and how this relates to clinical pain measures.
Abstract: The treatment of acute pain remains unsatisfactory despite advances in pain research and the publication of numerous guidelines. The aim of this study was to survey postoperative and emergency room acute pain treatment in Switzerland, particularly regarding compliance with practice guidelines on therapeutic responsibility, treatment algorithms, pain documentation, quality control and education.A representative sample of anaesthesiologists and surgeons (general and orthopaedic) was selected from all Swiss hospitals with regular surgical activity and sent a 256 point questionnaire on acute pain management. Five hundred and seventy five doctors were contacted in 98 hospitals, 44% of doctors (covering 89% of hospitals) returned fully completed questionnaires. Half the respondents work in a hospital with an acute pain service. For postoperative pain management, only 10% of prescription is by algorithm, less than a third of respondents regularly determine pain scores, only 15% perform any statistical analysis of pain management, less than one third regularly meet to discuss management problems, and half claim not to have received-or be receiving-formal (i.e. structured/accredited) pain education. The situation is even less satisfactory for emergency room analgesia. Respondents accept the contribution of postoperative and emergency room analgesia to reduced costs and improved medical outcomes. Asked to highlight their major concerns in acute pain management, lack of education and inadequate organisation are listed in first and second positions. This survey suggests that compliance with published practice guidelines for acute pain management can be improved, and highlights the need for continuing organisational and educational development in acute analgesia, particularly for the emergency room.
Abstract: Increased or decreased gain in central nervous system processing after surgery, i.e. neuroplasticity, may play an important role in postoperative pain. Identification of patient subgroups particularly vulnerable to either type of post-surgical neuroplasticity is thus of interest. Preoperative pain has also been suggested to increase vulnerability to post-surgical chronic pain complications due to central facilitation. To study if back pain preoperatively is associated with differences in central sensory processing, we measured transcutaneous electric sensation, pain detection and pain tolerance thresholds at the upper arm, lower back and lower leg in 52 consecutive patients scheduled for back surgery in a blinded, prospective fashion. Patients with no pain had significantly lower pain thresholds than patients with pain in the leg, and significantly higher pain thresholds than those with pain in the back. These results suggest that preoperative pain can induce diverse central neuroplastic changes, i.e. inhibition and facilitation, and that the nature of this neuroplasticity depends on the nature of the pain involved. The presence of facilitation may be the basis of the increased vulnerability described in some studies of patients with significant preoperative pain, whereas the implications of reduced pain sensitivity are less clear. The demonstration of neuroplasticity and its diversity are, however, likely to be of significant clinical relevance.
Abstract: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG).
Abstract: Chronic pain management by Swiss specialist physicians with the primary hypothesis that pain clinic practitioners conform better to good practice (interdisciplinarity, diagnostic/therapeutic routines, quality control, education) than other specialists treating chronic pain was surveyed. Management of all types of chronic pain by pain clinic practitioners and rheumatologists, oncologists or neurologists was compared via a mailed questionnaire survey (n=125/group). Two hundred and twenty-nine (46%) of 500 mailed questionnaires were returned with similar group return rates. Eighty-six percent of responders find chronic pain therapy very difficult/difficult; they estimate only 45% of these patients achieve good outcomes. Twenty-three per cent of responders belong to an interdisciplinary pain centre, but 72% of chronic pain patients are treated by responders alone. Fifty-nine percent never/only occasionally use therapeutic algorithms, 38% use formal pain diagnostic procedures, 20% have a pain quality control programme. Fifty-one percent lack past pain education, 37% do not attend continuing pain education, 69% agree that pain education is their greatest need. Pain clinic practitioners are more interdisciplinary and use more pain diagnostics than other specialists. They are matched by oncologists in education and success in therapeutic escalation, and bettered by them in algorithm use. Pain clinic practitioners and oncologists bring particular-differing-skills to chronic pain management compared to rheumatologists and neurologists. Chronic pain management diversity may result from differences in malignant and benign pain, and its generally being provided by the speciality treating the underlying cause. This survey identifies targets for improvement in areas fundamental to good chronic pain practice: interdisciplinarity, diagnostic/therapeutic tools, quality management and education.
Abstract: Anaesthesia for the surgical treatment of supratentorial tumours requires an understanding of: the pathophysiology of a localised or generalised increase in intracranial pressure (ICP), the regulation and maintenance of intracerebral perfusion, avoidance of secondary systemic insults to the brain, and the effects of anaesthetic drugs on ICP, cerebral perfusion and cerebral metabolism. Knowledge of the therapeutic options available for decreasing ICP, brain bulk and brain tension perioperatively is also essential. Potential complications which may present during supratentorial neurosurgery include massive intraoperative haemorrhage and seizures. The fact that the surgeon is operating on a tensed brain is also a potential source of difficulty. The need to monitor brain function and environment during surgery poses a challenge to the anaesthesiologist, as does the achievement of rapid emergence from anaesthesia with the adequate use of anaesthetic drugs.
Abstract: Nociception results in peripheral and central changes in sensory processing. These changes are considered to significantly contribute to postoperative pain and its outcome. Objective measures of changes in sensory processing are now being studied in humans after surgery. Surgical nociception leads to both central excitation (eg, spinal sensitization) and central inhibition (eg, descending inhibition), with inhibition being the dominant response during the first day or so after surgery. Analgesia commenced before surgery (preemptive analgesia) depresses central sensitization and enhances central inhibition. Patients operated on under nonanalgesic anesthesia may exhibit rebound central sensitization for up to 5 days postoperatively after the cessation of postoperative opioid analgesia. There is only a weak relationship between the described objective changes in sensory processing after surgical nociception and subjective clinical pain measures such as pain intensity scales or postoperative analgesic consumption.
Abstract: The pharmacodynamics of morphine-6-glucuronide (M-6-G) i.v. were assessed in 12 healthy male volunteers in an open study. After a single bolus dose of M-6-G 5 mg i.v., we measured antinociceptive effects, using electrical and cold pain tests, and plasma concentrations of M-6-G, morphine-3-glucuronide (M-3-G) and morphine. Pain intensities during electrical stimulation (at 30, 60 and 90 min after injection) and ice water immersion (at 60 min) decreased significantly (P < 0.005) compared with baseline. Mean plasma peak concentrations of M-6-G were 139.3 (SD 38.9) ng ml-1, measured at 15 min. Our data demonstrate that M-6-G has significant analgesic activity.
Abstract: We studied nociception-associated arousal following laryngoscopy and intubation in patients scheduled for elective open heart surgery, using EEG power spectra and hemodynamics. Either fentanyl (7 micrograms/kg; n = 30) or sufentanil (1 microgram/kg; n = 30) were given in a randomized fashion to induce anesthesia in heavily premedicated patients, followed by pancuronium bromide (100 micrograms/kg). EEG-power spectra (delta, theta, alpha, beta) as well as mean arterial blood pressure (MAP) and heart rate (HF) were measured at the following end-points: before the induction of anesthesia (control), 1 and 10 minutes after laryngoscopy and intubation (L & I). Linear regression analysis was computed to determine which of the EEG power spectra was most sensitive to detect insufficient blockade of nociceptive-related arousal when correlated with haemodynamics. In the fentanyl group the change in HF closely correlated with the decrease of power in the slow delta- and theta-domain (r2 = 0.98 and r2 = 0.89 respectively) of the EEG. The change in MAP also closely correlated with a decrease in the slow delta- and theta-domain (r2 = 0.97 and r2 = 0.99 respectively). There was little correlation in regard to spectral edge frequency (SEF) and HF and MAP changes (r2 = 0.36 and r2 = 0.12 respectively). In the sufentanil group the change in HF correlated closely with an increase of power in the fast alpha and a decrease in the slow theta-domain (r2 = 0.91 and r2 = 0.98 respectively) of the EEG. The changes in MAP closely correlated with an increase in the fast alpha-band a decrease in the slow theta-domain (r2 = 0.98 and r2 = 0.73 respectively). Also there was little correlation of SEF with HF and MAP changes (r2 = 0.09 and r2 = 0.02 respectively). Among the EEG-spectra, reduction of power in the slow delta- and theta-bands are the most sensitive parameters to determine insufficient antinociception of opioids commonly used for the induction in cardiac anesthesia. Increase of power in the alpha-band seems to be closely correlated with cortical reactivation and reduction of hypnosis, while a reduction of power especially in the deltabut more so in the theta-band of the EEG reflects nociception related arousal.
Abstract: We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.
Abstract: Drugs interacting with opioid or N-methyl-D-aspartate (NMDA) receptors may have differing effects on post-surgical sensory changes, such as central inhibition or spinal excitation. We compared the effect of supplementing isoflurane/N2O/O2 anesthesia with an opioid agonist (fentanyl [n = 15]) or two drugs inhibiting the NMDA system differently (magnesium, ketamine [n = 15 in each group]) on sensory changes after abdominal hysterectomy. Electric sensation, pain detection, and pain tolerance thresholds were determined (preoperatively and 1, 4, 24 h, and 5 days postoperatively) in arm, thoracic, incision, and leg dermatomes together with pain scores and cumulative morphine consumption. Thresholds relative to the arm were derived to unmask segmental sensory changes hidden by generalized changes. Absolute thresholds were increased 1-24 h, returning to baseline on Day 5, without overall differences among drugs. Fentanyl thresholds were lower 1 h and higher 5 days postoperatively compared with magnesium and ketamine; thresholds were lower at 24 h for magnesium versus ketamine. Relative thresholds increased compared with baseline only with fentanyl (1-4 h); none decreased. Pain scores and morphine consumption were similar. Thus, all adjuvants suppressed spinal sensitization after surgery. Fentanyl showed the most, and magnesium the least, central sensory inhibition up to 5 days postoperatively, with different patterns of inhibition directly postsurgery versus later. Differences in sensory processing were not reflected in clinical measures. Implications: We studied the effects on postsurgical sensory processing of general anesthesia supplemented by drugs affecting opioid or N-methyl-D-aspartate receptors using sensory thresholds. Generalized central sensory inhibition, differently affected by the drugs, predominated after surgery. All drugs suppressed spinal excitation. Clinical pain measures did not reflect sensory change.
Abstract: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant.
Abstract: Gastrointestinal motility may be considerably reduced by anaesthesia and or surgery resulting in postoperative ileus. Inhibition of propulsive gut motility is especially marked after an opioid-based technique. Little, however, is known of the gastrointestinal effects of the hypnotic propofol when given continuously over a longer period of time, which is the case in total intravenous anaesthesia (TIVA) and in intensive care sedation. We therefore set out to study the effects of a propofol-based nitrous oxide/oxygen anaesthesia (group PO) on gastro-caecal transit time. The results were compared with a propofol-ketamine technique (group PK) and an isoflurane-based anaesthesia (group I; each group n = 20).
Abstract: Managing postoperative nausea and vomiting (PONV) depends on awareness of the problem, the therapeutic measures available, and effective implementation control systems. We mailed 616 PONV questionnaires to all 129 Swiss hospitals with anesthesiological and surgical departments. The responses [192 (31%) completed questionnaires from 87 (67%) hospitals] are representative of Swiss hospital anesthesiologists and surgeons. Anesthesiologists' perceptions of PONV are closer to those found in the literature than surgeons'. More than three quarters of anesthesiologists and less than half of surgeons practice PONV prophylaxis. Half of the respondents are dissatisfied with present antiemetics. Anesthesiologists worry about the cost of PONV prophylaxis, and surgeons are concerned about their lack of theoretical knowledge. Formal PONV policies are rare, with little consensus on treatment responsibilities. Sixty percent of respondents document PONV occurrence, and less than 20% perform any formal PONV audit. This survey identifies factors amenable to improvement regarding PONV management in Swiss hospitals. PONV education is a necessity, particularly for surgeons. Cost needs to be addressed with anesthesiologists. The limited therapeutic efficacy of antiemetics is a concern. PONV management needs standardization, organization, consensus, and research. Better audits and visibility in patients' charts could further improve the quality of PONV management.
Abstract: We describe a case in which jugular venous bulb oxygen saturation (SjvO2) monitoring proved useful during the surgical resection of an intracranial arteriovenous malformation (AVM). Surgical resection of large intracranial AVMs may be followed by normal perfusion pressure breakthrough with brain swelling, hyperemia, and subsequent problems in achieving hemostasis. SjvO2 monitoring during AVM embolization by interventional radiology has been shown to help in deciding whether embolization is sufficient to avoid such postresection hyperemia, but its use during surgical resection has not been described. In the case discussed, SjvO2 monitoring enabled assessment of the risk of postresection hyperemia preoperatively and permitted the degree and completeness of surgical AVM resection to be followed intraoperatively. During the normal perfusion pressure breakthrough bleeding which followed complete AVM resection, SjvO2 monitoring helped with safe management of the controlled hypotension that finally permitted hemostasis to be achieved.
Abstract: NMDA receptor activation is considered one of the mechanisms involved in postoperative pain and hypersensitivity. Magnesium is the physiological blocker of the NMDA-receptor-complex-associated calcium ionophore. The aim of this study was to determine if a pre-, intra- and postoperative infusion of magnesium would reduce postoperative pain.
Abstract: The interaction between doxacurium and halothane, isoflurane or alfentanil has not been studied in children. Using the cumulative dose-response technique and electromyography, we determined ED50 and ED90 of doxacurium during halothane (n = 9), isoflurane (n = 12) or alfentanil (n = 9) based anaesthesia in children aged 2-10 years. Both isoflurane and halothane potentiated the effects of doxacurium compared to alfentanil. The ED50 for doxacurium/halothane was 23.9 micrograms.kg-1 compared to 32.7 micrograms.kg-1 for doxacurium/alfentanil. The ED90 for doxacurium/isoflurane was 32.7 micrograms.kg-1 compared to 48.2 micrograms.kg-1 doxacurium/alfentanil (p < 0.05). There were no significant time course differences between the groups. When equipotent doses of doxacurium were used to provide muscle relaxation the duration of the neuromuscular block was similar in children who received aflentanil, halothane or isoflurane supplementation of N2O/O2 anaesthesia.
Abstract: Nociception can produce segmental spinal sensitization or descending supraspinal antinociception. We assessed both types of sensory change after surgery during isoflurane-nitrous oxide anaesthesia with or without fentanyl before nociception. Patients undergoing back surgery received fentanyl 3 micrograms kg-1 (n = 15) or placebo (n = 15) before anaesthesia in a prospective, randomized, blinded study. Sensation, pain detection and tolerance thresholds to electrical stimulation were measured before operation at the arm, incision and herniated disc dermatomes (HDD) and 1, 2, 4, 6, 24 h and 5 days after operation, together with pain scores and patient-controlled morphine consumption (duration 24 h). For segmental effects, thresholds were normalized to the thresholds at a distant dermatome (arm). Raw pain thresholds were increased after operation (fentanyl > placebo) and were maximal at 4 h (pain tolerance in HDD: fentanyl +5.2 mA (+62.7%), placebo, +3.8 mA (+44.2%); P < 0.05 vs baseline for both). Normalized sensation thresholds decreased for placebo only (HDD/4 h: placebo, -1.8 (-44.8%), P < 0.05; fentanyl, +0.1 (+5.5%) ns). All changes returned to baseline by 24 h except for the placebo group normalized HDD sensation (d5: placebo, -2.4 (-59.7)%, P < 0.05; fentanyl -0.1 (-5.5%) ns). Pain scores and morphine consumption were similar. The study demonstrated both supraspinal analgesia and spinal sensitization after surgery. Fentanyl administration before operation augmented the former while decreasing the latter, and hence sensitization, especially if neuropathic, may particularly benefit from pre-emptive analgesia.
Abstract: The aim of this study was to investigate pain perception during thiopentone or propofol infusions for sedation. Thirty ASA 1 or 2 patients received a two step infusion of either thiopentone (step 1: 1.25 mg.kg-1 followed by 2.5 mg.kg-1.h-1; step 2: 1.25 mg.kg-1 and 12.5 mg.kg-1.h-1; n = 15) or propofol (step 1: 0.5 mg.kg-1, 1 mg.kg-1.h-1; step 2: 0.5 mg.kg-1, 5 mg.kg-1.h-1; n = 15) for sedation. At control and 10 min after the start of each infusion dosage, reaction times and thermal pain detection thresholds were determined. We found no clinically or statistically significant depression of thermal pain detection thresholds during propofol or thiopentone infusions and these are, therefore, unlikely to be associated with clinically relevant hyperalgesia.
Abstract: We have investigated the interaction between magnesium sulphate 40 mg kg-1 i.v. and vecuronium. First, we determined the effect of pretreatment with magnesium on the potency of vecuronium using a single bolus dose-response technique. In addition, we compared the time course of vecuronium-induced neuromuscular block (vecuronium 100 micrograms kg-1) with and without magnesium pretreatment. For both parts, neuromuscular block was assessed by electromyography. In addition, the effect of magnesium pretreatment on vecuronium-induced neuromuscular block was investigated in the context of rapid sequence induction of anaesthesia. We found that the neuromuscular potency of vecuronium was increased by pretreatment with magnesium sulphate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50: 21.3 vs 26.9 micrograms kg-1; ED90: 34.2 vs 45.7 micrograms kg-1; P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4-vecuronium group vs 297.3 (122) s for controls (P < 0.05). Clinical duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for controls; P < 0.05). This was also true for the recovery index (20.1 (6.6) min vs 10.6 (3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8 (6.9) min; P < 0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4, reaching the same quality as that with suxamethonium 1 mg kg-1. We conclude that magnesium pretreatment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular block.
Abstract: Pre-emptive analgesia is based on the idea that analgesia initiated before a nociceptive event will be more effective than analgesia commenced afterwards, and that its effects will outlast the pharmacological duration of action of the analgesic used. The idea of pre-emptive analgesia is based upon experimental neurophysiological work demonstrating that afferent nociceptive impulses result in alterations of central nervous system function. These changes, most easily elicited by C-fibre afferents, particularly affect the spinal dorsal horn. Termed central sensitisation, they are reflected by reduced pain thresholds (allodynia), increased responses to pain (hyperalgesia), after-discharging or spontaneous activity of dorsal horn neurons (wind-up), and extension of hypersensitivity to unaffected tissues (secondary hyperalgesia). Their biochemical basis is now being unravelled, with excitatory amino acid (e.g. NMDA) and neuropeptide (e.g. substance P) neurotransmitters playing prominent roles. Blockade of these receptors has recently been shown to depress the central sensitisation associated with nociception. Ketamine, a non-competitive NMDA receptor blocker, for example, has been shown modulate postoperative pain in a positive way. Although the existence of central sensitisation is now being clinically demonstrated, studies of pre-emptive analgesia in the surgical context have not revealed clinically significant effects. This is probably because surgical nociception is much longer-lasting, multimodal and intense than its experimental counterparts. Clinical studies have so far only used short-term analgesia. To permit extrapolation from the experimental to the clinical situation, pre-emption in the surgical context must correspond adequately to the duration and extent of the nociception involved. Studies of pre-emptive analgesia in a clinically relevant form, i.e. where nociception and analgesia are correctly matched, are called for.
Abstract: We studied EEG arousal after laryngoscopy and intubation with standardized bolus induction of anaesthesia. Twenty patients were prospectively allocated randomly to induction with propofol 3 mg kg-1 (n = 10) or thiopentone (6 mg kg-1 (n = 10) and 50% nitrous oxide in oxygen. Neuromuscular block was produced with vecuronium 0.2 mg kg-1 given 30 s after induction. Three minutes after induction, laryngoscopy was performed for 60 s, with intubation at 3 min 30 s, and study end at 5 min. Nociception to laryngoscopy and intubation was followed by loss of low (relative delta activity change: thiopentone -30%, propofol -7%; P < 0.05) and a shift to higher frequency EEG activity (beta activity change: thiopentone +647%, propofol +61%; P < 0.05). This EEG arousal was greater in the thiopentone group, despite the fact that EEG depression was similar to that produced by propofol before laryngoscopy and intubation. Propofol and thiopentone in combination with nitrous oxide had similar cortical depressant effects, but propofol appeared to depress subcortical nociceptive processing more than thiopentone. While the degree of cortical EEG depression seems less useful for predicting reaction to subsequent nociception, EEG arousal reactions may prove suitable for monitoring intra-anaesthetic nociception and its modulation.
Abstract: In order to explain the reported shorter clinical duration of action of cumulative ED95 of pipecuronium in infants as compared to children or adults, the pharmacokinetic profiles of pipecuronium were compared in infants (n = 6; mean age 6.8 months; mean weight 7.3 kg) in children (n = 6; mean age 4.6 years; mean weight 19.2 kg) and in adults (n = 7; mean age 42 years; mean weight 58.2 kg). Equipotent doses (2 x ED95) of pipecuronium were injected i.v. as single bolus and arterial blood was sampled for 4-5 h. Pipecuronium was quantified by complex formation with [125I]-labelled rose bengal. Pharmacokinetic parameters were calculated using a two-compartment open model. The median for the distribution half-life of pipecuronium was 2.54 min (interquartile range: 1.0-2.5 min) in infants and 2.04 min (0.26-2.04 min) in children; both were significantly shorter than in adults (5.75 [3.7-9.7] min). The plasma clearance of pipecuronium was significantly decreased in infants (1.50 [0.6-1.5] ml.min-1.kg-1; P < 0.05) as compared to children and adults (2.27 [0.88-2.27] and 2.45 [1.7-3.2] ml.min-1.kg-1, respectively). The total volume of distribution was similar in all three groups. We conclude that the pharmacokinetic features of pipecuronium are age-dependent: differences as compared to adults consisted of a faster distribution in both infants and children and a slower elimination in infants. The pharmacokinetic profile of pipecuronium does not explain the faster recovery from neuromuscular blockade in infants as compared to children. Because of the low total plasma clearance in infants, pipecuronium dosage should be carefully monitored to avoid accumulation and prolonged paralysis.
Abstract: Status epilepticus is one of the most frequent neurological emergencies in the intensive care unit. Standard treatment includes intravenous barbiturates, benzodiazepines and phenytoin. However, drug coma is sometimes necessary to control refractory status epilepticus. We report such a case, successfully treated by intravenous propofol coma to EEG burst suppression.
Abstract: Pruritus is a severe and troublesome symptom in patients with cholestasis and is often difficult to treat. Propofol was recently shown to be efficient in the treatment of pruritus secondary to spinal morphine administration. In a prospective, randomized, double-blind, cross-over and placebo controlled study, 20 patients received 1 dose of propofol (15 mg) and 1 dose of Intralipid (1.5 mg) during a 2-day study period. Pruritus was assessed by a visual analogue scale from 0 (no pruritus) to 10 (most severe pruritus imaginable). Treatment success was defined as a decrease in pruritus of at least 4 points on the scale in 80% of the patients receiving propofol and in 15% of those receiving intralipid (p < 0.05). Discomfort on injection was observed in 15% under propofol treatment. In conclusion this study shows that subhypnotic doses of propofol are effective for the short-term symptomatic relief of pruritus associated with liver disease. At the dose administered, side effects were rare and minor.
Abstract: Propofol is an intravenous anesthetic agent with a short half-life allowing rapid recovery; it has cerebral hemodynamic effects similar to those of thiopental. The aim of the present study was to describe 83 patients (mean age 50.6 +/- 15.1 yrs) scheduled for intracranial surgery in whom a total intravenous anesthesia technique (TIVA) with propofol was used. 16 patients were operated in the sitting position. Mean propofol induction dose was 2.1 +/- 0.8 mg/kg combined with 2.3 +/- 1.8 micrograms/kg of fentanyl, 1.5 mg/kg of lidocaine, and 0.08 mg/kg of vecuronium to facilitate intubation. Before installation of the Mayfied pin-head holder, the site of the pins was infiltrated with 2-3 cc of lidocaine 1%. Anaesthesia was maintained with propofol 5.9 +/- 2.1 mg/kg/h and fentanyl 1.6 +/- 0.65 micrograms/kg/h. Mean values of mean arterial pressure and heart rate showed less than 10% variation at intubation, application of the pin-head holder and skin incision. Intracranial pressure measured by the lumbar route (after checking the patency of the CSF passage from the cerebral to the spinal compartments) varied by slightly more than 10%, starting at 11.3 +/- 6.0 mmHg before induction and 11.3 +/- 5.2 mmHg at intubation down to 9.5 +/- 4.5 mmHg after skin incision. The lumbar drainage in place allowed the surgeon to improve brain relaxation by drawing 5-20 cc of lumbar CSF. Duration of anaesthesia was 367 +/- 96 mn from induction to extubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: In a prospective, randomized, double-blind clinical trial, we compared the efficacy of propofol and naloxone for the treatment of spinal-morphine-induced pruritus. Forty patients presenting with severe pruritus within 24 h of epidural morphine administration were allocated to receive either propofol 10 mg intravenously (i.v.) or naloxone 2 micrograms/kg. In the absence of a positive response, a second dose of the same treatment was given 5 min later. Pruritus and the level of post-operative pain were assessed every 5 min up to the end of the study period (45 min) using a verbal rating scale. The overall success rate in treating pruritus was similar in the two groups (80%). The rate of success after the first injection of the treatment drug was also similar (55%). The level of postoperative pain decreased after drug treatment in six patients (30%) in the propofol group versus none in the naloxone group (P < 0.05). Forty-five percent of the patients in the naloxone group had an increase in the level of postoperative pain versus none in the propofol group (P < 0.05). In conclusion, these results suggest that propofol and naloxone are equally effective in treating spinal-morphine-induced pruritus. However, the level of postoperative pain is significantly less in the propofol group.
Abstract: We believe that today balanced TIVA represents the best anesthetic technique for neurological surgery. Freely acknowledging that this point of view is unproven (36) with regard to the hard criterion of patient outcome on leaving the hospital, we submit that the intermediate or surrogate criteria discussed make a convincing case for preferring TIVA to volatile-based anesthetic techniques. Until a study demonstrating hard outcome differences between the two techniques is achieved, we will continue to encourage the use of TIVA in neuroanesthesia, based on its practical (anesthetic depth, neuromonitoring, surgical field) and theoretical (homeostasis, metabolism, antinociception, neuroprotection) advantages.
Abstract: We investigated the prophylactic antiemetic effect of added low-dose infusion of propofol in patients exhibiting nausea and vomiting refractory to dexamethasone and serotonin antagonist during non-cisplatin chemotherapy for breast cancer. In a prospective open longitudinal study, 117 patients who had more than five episodes of nausea and vomiting in their first chemotherapy cycle during the first 24 hr completed the study. They received in addition to the usual prophylactic antiemetic regimen a continuous intravenous infusion of 1 mg.kg-1.hr-1 propofol started four hours before chemotherapy and continued up to 24 hr for the two subsequent cycles. The number of vomiting/nausea episodes, level of sedation, patient activity, appetite and preference for future chemotherapy cycles were assessed. In the propofol supplemented cycles 90 and 80% of patients, during the 1st and 2nd propofol-assisted cycle respectively, were free of nausea and vomiting during the first 24 hr after chemotherapy. Patients were more frequently active and had more appetite during the propofol-assisted cycles. No propofol-associated side effects were observed. We conclude that the addition of a subhypnotic infusion of propofol enables better control of nausea and vomiting caused by non-cisplatin chemotherapy in the first 24 hr post-treatment.
Abstract: The postoperative combination of epidural sufentanil and epidural droperidol was assessed in 40 patients with hip or knee arthroplasties. Patients were given a single intravenous (i.v.) bolus of sufentanil 50 micrograms with either droperidol 2.5 mg or placebo (0.9% NaCl) epidurally in a double-blind, randomized design at the first request for postoperative analgesia. Pain scores, side effects, and sufentanil plasma concentrations were regularly assessed for 5 h after injection. Heat pain thresholds were measured pre- and postoperatively. The incidence of nausea, emesis, and pruritus associated with epidural sufentanil was decreased by epidural droperidol (P < 0.01, P < 0.001, P < 0.05, respectively). More patients were sedated with epidural droperidol than with placebo (P < 0.02). The initial reduction in pain scores was similarly profound, but the duration of analgesia after sufentanil and droperidol was significantly shorter than after sufentanil and placebo (P < 0.02). Phasic and tonic heat pain thresholds were increased postoperatively 1 h after sufentanil and placebo (P < 0.01 and P < 0.0005, respectively). Only the tonic heat pain thresholds were increased 1 h after sufentanil and droperidol (P < 0.002). The addition of epidural droperidol significantly reduced the excitatory side effects of epidural sufentanil while diminishing the duration of analgesia. These interactions may be of clinical significance in reducing the toxicity of opioids, but the effect on duration of analgesia must be considered when repeated doses of opioids are prescribed.
Abstract: Pruritus is a severe and troublesome symptom in patients with cholestasis and is often difficult to treat. Propofol was recently shown to be efficient in relieving pruritus secondary to spinal morphine administration. The efficacy of propofol was therefore investigated in patients with pruritus associated with liver disease.
Abstract: Spontaneous excitatory movements have been observed during recovery from propofol anaesthesia in children. Epilepsy has been postulated as a possible mechanism to explain these movements. We report the first case in which these spontaneous excitatory movements were studied using simultaneous multichannel EEG recordings.
Abstract: 20 consecutive patients with nausea and vomiting secondary to cisplatin chemotherapy uncontrolled by serotonin-antagonist and corticosteroid prophylaxis during their first cycle received adjuvant propofol. This new anesthetic agent was added at subhypnotic doses, i.e. 1 mg/kg/h, as a continuous intravenous infusion during the two subsequent chemotherapy cycles. In 85 and 90% of patients, nausea and vomiting were prevented in the first 24 h following the first and second propofol-supplemented chemotherapy cycles respectively. 24-72 h postchemotherapy, this side effect remained suppressed in 75 and 70% of patients, respectively. Patients' comfort and appetite were improved. All 20 subjects preferred the propofol-containing regimen.
Abstract: Nausea and vomiting associated with cisplatin chemotherapy is a source of major morbidity that remains difficult to control. Acute phase (0-24 hours after induction of chemotherapy) nausea and vomiting parallels plasma serotonin release, which explains the effectiveness of 5HT3 antagonists; serotonin release in the delayed phase (24-48 hours after induction), during which consistent antiemetic control remains elusive, has not been investigated. The effect of propofol, a recent addition to the antiemetic armamentarium, on this serotonin release has not been studied.
Abstract: Owing to the recent advances of bioelectric signals computerized treatment a real monitoring of anaesthesia is now possible, either by EEG or by classical or event-related evoked potentials methods. Available methods and their indications and difficulties are discussed with the help of some clinical examples.
Abstract: We investigated the efficacy of subhypnotic doses of propofol for spinal morphine-induced pruritus in a prospective, randomized, double-blind, placebo-controlled study. Fifty patients, ASA physical status 1-3, with spinal morphine-induced pruritus were allocated to receive either 1 ml propofol (10 mg) or 1 ml placebo (Intralipid) intravenously after gynecologic, orthopedic, thoracic, or gastrointestinal surgery. In the absence of a positive response, a second drug treatment was given 5 min later. The persistence of pruritus 5 min after the second treatment dose was considered a treatment failure. All failures then received, in an open fashion, a supplementary dose of propofol (10 mg) and were reevaluated 5 min later. Both groups were well matched. The success rate was significantly greater in the propofol group (84%) than in the placebo (16%) group (P less than 0.05). Ninety percent of the treatment failures in the placebo group were successfully treated by a supplementary dose of 10 mg propofol. Eight percent of the patients (4% in each group) were resistant to all treatments, including naloxone 0.08 mg intravenously. Three patients had a slight increase in sedation in the propofol group versus none in control (not significant). The beneficial effect of treatment was longer than 60 min in 85% of patients in the propofol group and in 100% of the controls (not significant). These results suggest that propofol in a subhypnotic dose is an efficient drug treatment for spinal morphine-induced pruritus. At the dose administered (10 mg), side effects were rare and minor.
Abstract: Hepatic cholestatis is frequently associated with pruritus. This pruritus is often intractable and resistant to conventional treatment. We treated three patients with intractable cholestatic pruritus with subhypnotic doses of propofol, a new intravenous anesthetic induction agent. All patients rapidly became itch- and scratch-free for a period of 60-90 min. No sedation occurred; no other side effects were observed.
Abstract: Propofol is associated with a low incidence of postoperative nausea and vomiting. In a prospective, randomized, double-blind, placebo-controlled study, we investigated the possible direct antiemetic properties of a subhypnotic dose of propofol. Fifty-two ASA physical status I or II patients, aged 15-60 yr with nausea and vomiting after minor gynecologic, orthopedic, or digestive tract surgery, were included in the study and received either propofol (10 mg = 1 mL) or placebo (1 mL Intralipid) intravenously in the postanesthesia care unit. Patients treated with propofol experienced a larger reduction in nausea and vomiting than patients treated with placebo (81% vs 35% success rate; P less than 0.05). Patients successfully treated had a similar incidence of relapse (propofol 28%; placebo 22%) within the first 30 min after therapy. Thirty-three percent of the propofol-treated patients and 44% of the placebo-treated patients showed a minor increase in sedation. The level of postoperative pain did not change in either group. Hemodynamic values remained unchanged in both groups. Pain on injection (7.6%) or dizziness (3.6%) only occurred in the propofol group. We conclude that propofol has significant direct antiemetic properties.
Abstract: The haemodynamic effects of propofol (2 mg/kg), etomidate (0.2 mg/kg) and thiopentone (4 mg/kg) were studied in 30 ASA 1 and 2 patients in whom anaesthesia had been induced with midazolam 0.1 mg/kg, fentanyl 5 micrograms/kg, vecuronium 0.1 mg/kg and atropine 10 micrograms/kg, and maintained with nitrous oxide in oxygen. Arterial pressure was measured directly and left ventricular diameters were determined by transoesophageal echocardiography. Systolic blood pressure after propofol and thiopentone and the end-systolic quotient (systolic pressure/end-systolic diameter), a measure of inotropy, decreased. Fractional shortening (end-diastolic-end-systolic diameter/end-diastolic diameter) decreased only in the thiopentone group. Diastolic blood pressure and end-diastolic diameter (a measure of preload) did not change in any of the groups, and the etomidate group showed no changes in the haemodynamic variables measured. Propofol shows simultaneous negative inotropy and afterload reduction, while thiopentone is exclusively negatively inotropic.
Abstract: Epidural morphine is effective in the treatment of postoperative pain, but the incidence of associated side effects is high. To assess a potential reduction of opioid side effects by droperidol, 4 mg morphine with either placebo or 2.5 mg droperidol was injected epidurally in a double-blind, randomized, postoperative trial. Forty patients undergoing hip replacement surgery were studied. The overall incidence of side effects during the first 24 h in the group receiving droperidol and morphine was less than 50% of that in the group receiving placebo and morphine (P less than 0.008). Pruritus, emesis, nausea, urinary retention, and hypotension were diminished in the group with droperidol. No significant differences in duration or quality of analgesia were seen. Epidural injection of droperidol did not result in any local or systemic side effects.
Abstract: In a prospective clinical study we followed up 697 patients operated upon under spinal anaesthesia to determine the incidence of, and the factors predisposing to, post-spinal backache. The incidence of post-spinal backache, which occurs in approximately one in seven patients (13.1%) is comparable to that of post-spinal headache. This often neglected additional cause of post-spinal morbidity can be reduced by the use of atraumatic techniques and with small-gauge spinal needles for performing lumbar puncture.
Abstract: In a prospective clinical study we followed 320 patients operated upon in spinal anesthesia. We were especially interested in headache patterns after spinal anesthesia and their causes, with particular reference to the local anesthetic used. Apart from the typical postspinal headache due to low cerebrospinal fluid (CSF) pressure, we found a nontypical pattern which was considerably more prevelant than the classical type. The typical postspinal headache correlated well with procedures (multiple perforations, thicker cannulae) that lower or prolong the reduction of CSF pressure and a history of migraine. The nontypical headache correlated with the use of lignocaine/articaine for spinal anesthesia, possibly due to metabolic and structural factors.
