Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 'chain-of-survival' concept has gained general acceptance in the care of cardiac arrest victims. Most standards and guidelines for cardiopulmonary resuscitation, however, focus on the initial links in the chain. We consider appropriate in-hospital care for the survivors a logical extension of the chain of survival. In recent years extensive research activity has probed the pathophysiology and pharmacology of postischemic reperfusion. The present review discusses the current understanding of mechanisms for cerebral damage following global ischemia. Promising pharmacological principles for protection or resuscitation from cerebral ischemia are reviewed. None of them are considered ready for clinical application. Clinical guidelines are proposed, based on the reviewed data and previously published clinical observations. Cornerstones of the proposed brain-oriented intensive care protocol are: (1) hemodynamic monitoring and meticulous treatment of circulatory disturbances, (2) controlled ventilation providing normoventilation and normoxia to all comatose patients, (3) avoiding hyperglycemia and hyperthermia in comatose patients, (4) adequate analgesia and sedation, tempered by the understanding that oversedation impedes neurological evaluation without promoting recovery. An accurate prognosis can usually be made 48-72 h after resuscitation. This permits reevaluation and assignment to an appropriate level of continued hospital care.
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PMID:Brain-oriented intensive care after resuscitation from cardiac arrest. 829 Aug 16

The influence of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]-carbonyl]-L-histidyl-L-prolinamide dihydrate), a new thyrotropin releasing hormone (TRH) analogue, on morphine-induced hypothermia, development of cerebral ischemia and analgesia was investigated in rodents. YM-14673, in doses not affecting the normal rectal temperature, antagonized morphine-induced hypothermia in mice. Morphine-induced hypothermia was also antagonized by administration of TRH, in doses increasing normal rectal temperature. Morphine increased the appearance rate of convulsions in rats subjected to bilateral occlusion of the carotid artery. YM-14673, unlike TRH, reduced the appearance rate of convulsions increased by morphine in the ischemic rats. Morphine-induced analgesia measured by the hot plate method was not affected by both YM-14673 and TRH. Naloxone antagonized the effect of morphine in the 3 models. These results suggest that YM-14673 possesses physiological opioid antagonistic properties.
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PMID:Effects of YM-14673, a new TRH analogue, on responses to morphine in rodents. 251 20

Eight-five carotid endarterectomies were performed in 77 patients, under regional anaesthesia using 2 different techniques: cervical epidural anaesthesia (35 cases) and cervical plexus block (50 cases). The patients' mean age was 71 years; 80 per cent had arterial hypertension and 41 per cent coronary disease. Transoperative cerebral ischaemia was detected by a 5-minute carotid clamping test, the occurrence of a neurological event indicating that shunting was required. In 62 patients this test was combined with measurement of carotid back pressure. None of the patients needed general anaesthesia. Intraoperative neurological events occurred more frequently (P less than 0.01) when the carotid back pressure was 25 mmHg or less, and 12 temporary shunts were installed for that reason (14.1 per cent). Three neurological events occurred at the end of endarterectomy: no shunt was installed and complete recovery was observed immediately after declamping. No complications ascribable to the anesthetic techniques were recorded. Mortality was nil, and the only neurological morbidity was a brachio-facial deficit which left few sequelae. The frequency of intra- or postoperative arterial hypertension was similar in both groups. Intraoperative hypotension, frequent under epidural anaesthesia, was observed in only one patient who had brachial plexus block (P less than 0.01). The analgesia obtained was equally good with both anaesthetic techniques, but cervical plexus block anaesthesia is easier to perform, had less haemodynamic repercussions and therefore tends to be preferred to cervical epidural anaesthesia. The lack of mortality, low morbidity and absence of systemic complications in this series despite the high number of patients at risk are in favour of this type of anaesthesia, notably for such patients. Moreover, because vigilance is preserved attention can be paid to the quality rather than the rapidity of endarterectomy, which is the best way of preventing embolism.
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PMID:[Carotid surgery under locoregional anesthesia]. 253 1

Dextromethorphan is one of the most widely used non-opioid cough suppressants, representing the active ingredient in several over-the-counter antitussive formulations. It does not possess the CNS pharmacology of other opiates in humans (i.e. analgesia, respiratory depression, abuse liability or psychotomimetic properties), but since the discovery in 1981 of high affinity recognition sites in brain for dextromethorphan a unique neuropharmacological profile has emerged for this relatively innocuous drug. Anticonvulsant and neuroprotective properties have been demonstrated, and treatment with dextromethorphan has been shown to improve the cerebrovascular and functional consequences of global cerebral ischemia. Frank Tortella and colleagues review the CNS pharmacology of dextromethorphan, its possible involvement with NMDA or sigma-receptors, and the potential clinical importance of this old 'new' drug.
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PMID:Dextromethorphan and neuromodulation: old drug coughs up new activities. 215 97

The course of ischemic increase of extracellular potassium concentration ([K+]e) was studied in rat cerebral cortex with potassium selective microelectrodes and correlated to the preischemic functional and metabolic state. Complete cerebral ischemia was induced in artificially ventilated rats by cardiac arrest. Seven different functional states including conditions with cerebral hypermetabolism (seizures, amphetamine intoxication, hyperthermia) and hypometabolism (barbiturate anesthesia, hypothermia) were chosen in order to cover a wide range of cerebral metabolic rates (CMRO2 : 28.7--2.4 ml O2/(100 g)/min). The ischemic increase of [K+]e was delayed in conditions with low CMRO2 and accelerated in conditions with high CMRO2; the time interval to the terminal steep rise in extracellular potassium concentration varied within the extremes of 35 +/- 5 and 365 +/- 12 sec (means +/- S.E.M.), the control state (N2O-analgesia) being 116 +/- 5 sec. In groups with high CMRO2 electrocortical activity ceased within 15 sec and in groups with low CMRO2 within 22 sec. The rates of the ischemic [K+]e increase, measured as rate of change in the potassium electrode potential (mV/sec), remained high in conditions with high preischemic CMRO2 and low in conditions with low CMRO2, indicating a remaining influence of the preischemic metabolism on membrane ion permeability. These results support previous metabolic data indicating that the rate of consumption of high energy phosphates during ischemia mirrors the preischemic cerebral metabolic rate. Phenobarbital anesthesia did not change the initial rate of [K+]e increase but reduced the rate of [K+]e increase later during ischemia, suggesting a special effect of barbiturates on partly depolarized membranes.
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PMID:The increase in extracellular potassium concentration in the ischemic brain in relation to the preischemic functional activity and cerebral metabolic rate. 740 19

Trauma is the leading cause of mortality in children between the ages of 1 and 14 years. It represents a major health problem in all industrialized countries. A well coordinated organization of the whole chain of cares is essential, from the initial management at the scene of the accident until the long term neurological rehabilitation of the child. During the initial examination, the presence of anoxia, hypovolemia or neurological distress was systematically evaluated. Emergency therapeutic measures should be ensured. At the term of this initial management: if the haemodynamic state is unstable, an emergency operative procedure may be required; if the haemodynamic state remains stable, one can realize a complete clinical and radiological assessment. The clinical and biological supervision must continue during this evaluation while sedation and analgesia are essential to limit an increase in intracranial pressure (ICP). At the term of this complete assessment, if one or several surgical lesions are identified, an operative program with a precise hierarchy is scheduled; if an intensive medical support is required, the child is then transferred to the pediatric intensive care unit. Most often, children with a serious head trauma do not have neurosurgical lesions but a "brain-swelling" or cerebral edema. Elevated ICP is one of the main risk for cerebral ischemia. Therefore, continuous assessment of ICP is essential. Thoracic trauma is most often a closed trauma in the child: pneumothorax and pulmonary contusion are the problems most frequently met. An emergency laparotomy is required if the abdomen volume increases rapidly associated to the persistence of a unstable haemodynamic status despite an important fluid expansion. However, the presence of intraperitoneal blood is no longer a formal indication to surgery. Frequent examination of liver and splenic lesions with abdominal tomodensitometry allows to avoid surgery in more than 90% of cases at the price of a very rigorous haemodynamic supervision. Intestinal perforations are rare and difficult to diagnose: peritoneal dialysis, if it reveals the presence of a leucocytosis greater than 500/mm3 or bacteria justifies the surgery.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Polytraumatised children]. 784 20

There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved.
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PMID:Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. 844 13

The goal of therapy in patients with severe head injury is to avoid secondary brain damage. Analgesia and sedation are an essential part of the therapy, and several drugs are in current use. However, few controlled clinical trials have been performed so far, and none of these drugs has proved to be superior. Although in the past the therapy has been focused on controlling elevated intracranial pressure (ICP), many authors emphasize the role of cerebral ischaemia in the prognosis of patients. Therefore, cerebral perfusion pressure (CPP) i.e. the difference between ICP and mean arterial pressure (CPP = MAP-ICP), seems to be more important than ICP alone. Analgesics and sedatives reduce the cerebral metabolic rate (CMR), and the consequent decrease in cerebral oxygen uptake might prevent ischaemic damage in regions with low perfusion. Moreover, a decrease in CMR is often associated with a decrease of cerebral blood flow (CBF) in regions with normal perfusion and, as a result, ICP is also reduced. Basically, the cerebral effects (on ICP, CMR, and CBF) and the haemodynamic effects with respect to maintenance of a sufficient CPP are most important in the selection of drugs for analgosedation. In addition, the effects on general intensive care management must be considered (pulmonary function, immunreactivity bowel motility). The purpose of this paper is to describe drugs commonly used for analgosedation in severe head injury. Barbiturates bring about the most pronounced decrease of CMR and ICP. In the past these drugs were used routinely in high doses ("barbiturate coma"). However, no improvement in outcome was demonstrable, and vitally dangerous side effects, such as infection, pulmonary dysfunction, arterial hypotension, and renal failure often occurred. High-dose barbiturate therapy is therefore only indicated in exceptional cases, such as refractory increase in ICP with preserved CO2 response of cerebral vessels. The effect is dependent on CMR at the start of this therapy. Benzodiazepines are frequently used in patients with head injury. They cause only a moderate decrease of CMR and ICP. In general, side effects are negligible. However, a possible decrease of MAP by reduced central sympathetic drive has to be taken into account. Opioids are also frequently used in patients with head trauma. The observed cerebral effects are inconsistent. Some authors have described increases in ICP, CBF, and CMR, but in most studies no influence on these values, or a decrease, has been observed. In any case, cautious titration of these drugs and cerebral monitoring are therefore desirable. As with benzodiazepines, a decrease in MAP due to central effects is possible. In addition, opioids inhibit bowel motility. Ketamine is generally used because of its favourable circulatory effects, bronchodilatation and absence of inhibition of bowel motility. In patients with increased ICP, however, it is often considered contraindicated, since it can be associated with cerebral vasodilation and ICP increase. Other studies did not confirm an increase of ICP when controlled ventilation and additional sedation were applied. More recent studies have demonstrated the role of neuroexcitatory NMDA-receptors in ischaemic and traumatic brain damage. Since ketamine exerts an antagonistic effect on N-methyl-D-aspartate receptors (NMDA) and studies in animals have demonstrated a protective effect of ketamine against ischaemic and traumatic brain damage, controlled clinical studies in patients with head injury are desirable. Propofol results in a profound decrease of CMR and a significant decrease of ICP, but often also in haemodynamic depression. Few results obtained during long-term administration are available, but it seems to be beneficial. More clinical studies are warranted. Gamma-hydroxybutyrate (GHB) is a physiological substance, which has only sporadically been investigated for sedation in patients with head trauma. The few available studies show beneficial res
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PMID:[Analgesia and sedation in patients with head-brain trauma]. 859 67

Puerperal women are reported to have a rate of cerebral infarction 13 times greater than non-pregnant females. We report a case of cerebral ischaemia in a 30-yr-old healthy parturient after epidural analgesia for labour, complicated by dural puncture treated with two epidural blood patches. Investigations showed the development of cerebral ischaemia on postpartum day 14. A transcranial Doppler ultrasonography showed vasospasm of the left middle cerebral artery still present at 3-month follow-up. At 1-yr follow-up, the patient had homonymous hemianopsia. We discuss the possible causative mechanism of the cerebral ischaemia in relation to the dural puncture and epidural blood patch.
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PMID:Postpartum cerebral ischaemia after accidental dural puncture and epidural blood patch. 1248 90

There are now four types of opioid receptors. The new designations OP(1), OP(2) and OP(3) correspond, respectively, to the classic delta-, kappa- and micro-nomenclature. OP(4) was previously known as ORL(1), the receptor for the endogenous heptadecapeptide nociceptin/orphanin FQ. Although the cellular effects of nociceptin resemble those of conventional OP(1), OP(2), and OP(3) opioid agonists, its effects on nociceptive processes are quite different. Nociceptin produces spinal analgesia but appears to antagonize the effects of opioids. Following the recent synthesis of the nonpeptide OP(4) agonist Ro-64-6198 by Hoffmann-La Roche and the nonpeptide OP(4) antagonist J-113397 by Banyu, the nociceptin-OP(4) system now represents a viable and intriguing new target for drug design. OP(4) agonists may be of use in the management of neuropathic pain, anxiety, anorexia, epilepsy, drug dependence, male impotence, hypertension, cerebral ischemia and neurogenic bladder. They may also serve as novel diuretics and to help to reduce gastrointestinal motility. OP(4) antagonists may be of use as general analgesics and in the improvement of memory function. This review covers the recent exciting progress in this field, compares the actions of OP(4) agonists and antagonists with those of classic opioids, and seeks to predict some of the untoward effects that may be seen with such drugs.
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PMID:The nociceptin receptor as a potential target in drug design. 1281 96


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