Contemporary management of neuropathic pain for the primary care physician

Neuropathic pain (NP), caused by a primary lesion or dysfunction in the nervous system, affects approximately 4 million people in the United States each year. It is associated with many diseases, including diabetic peripheral neuropathy, postherpetic neuralgia, human immunodeficiency virus-related disorders, and chronic radiculopathy. Major pathophysiological mechanisms include peripheral sensitization, sympathetic activation, disinhibition, and central sensitization. Unlike most acute pain conditions, NP is extremely difficult to treat successfully with conventional analgesics. This article introduces a contemporary management approach, that is, one that incorporates nonpharmacological, pharmacological, and interventional strategies. Some nonpharmacological management strategies include patient education, physical rehabilitation, psychological techniques, and complementary medicine. Pharmacological strategies include the use of first-line agents that have been supported by randomized controlled trials. Finally, referral to a pain specialist may be indicated for additional assessment, interventional techniques, and rehabilitation. Integrating a comprehensive approach to NP gives the primary care physician and patient the greatest chance for success.     

Delirium in older cardiac surgery patients: directions for practice

Delirium affects approximately 20% to 25% of patients undergoing cardiac surgery and is particularly common in older adults. This article reviews the etiology and risk factors for delirium associated with cardiac surgery in older adults. Delirium screening, prevention, and treatment strategies, including both pharmacological and nonpharmacological therapies, are presented. Interventions appropriate in both the intensive care unit and     

The treatment of depression in cancer patients: a systematic review

Goals of the work: To evaluate the efficacy of pharmacological and nonpharmacological treatments for depression in cancer populations. Materials and methods: The Supportive Care Guidelines Group conducted a systematic review of the published literature through June 2005. Search sources includes MEDLINE, EMBASE, CINAHL, PsycInfo, and the Cochrane Library. Comparative studies of treatments for depression in cancer patients were selected for review by two group members based on predefined criteria. Main results: Seven trials of pharmacological agents and four of nonpharmacological interventions were identified. Two trials detected a significant reduction in depressive symptoms for mianserin compared with placebo, and one trial found alprazolam to be superior to progressive muscle relaxation. Four drug trials found no significant difference between groups on depression measures although posttreatment reduction of symptoms was observed for all groups in two trials comparing active treatments (fluoxetine vs desipramine and paroxetine vs amitriptyline). Of the four trials involving nonpharmacological therapies for the management of depression, two detected a benefit for treatment (a multicomponent nurse delivered intervention and an orientation program) over usual care. Conclusion: There is limited evidence for the effectiveness of pharmacological and psychosocial interventions in the treatment of cancer patients with depressive disorders, and no evidence for the superiority of one treatment modality over another. Based on evidence from the general population and other medically ill populations, combined approaches to the treatment of depression may be the most effective. Further research is necessary in cancer patients to determine the relative effectiveness of psychosocial, pharmacological, and combined treatments. A paper presented as an invited lecture at the MASCC/ISOO 18th International Symposium of Supportive Care in Cancer in Toronto, Canada, June 2006, was based in part on this review. A complete list of Supportive Care Guidelines Group members is available at: .     

Delirium, depression, and other psychosocial and neurobehavioral issues in cardiovascular disease

Understanding relevant psychosocial (neural, behavioral, psychiatric) issues is essential to optimal care of individuals who have cardiovascular disorders. Delirium, a condition of diffuse cerebral dysfunction caused by underlying systemic or central nervous system pathology, and often requiring measures of acute neurobehavioral management with nonpharmacological and pharmacological means, in addition to treatment of the underlying medical disorder, often occurs in association with severe cardiovascular disease. Depression is a psychiatric disorder known to be associated with cardiovascular disease. Substantial improvement in understanding the nature of this association has occurred in the past 10 to 20 years, including very preliminary data suggesting that pharmacological treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants might improve postmyocardial infarction cardiac prognosis. Numerous other factors-anxiety, stress, social support, anger, and other personality factors-also are implicated in the relationship of psychosocial issues to cardiovascular disease.     

Optimal management of shivering during therapeutic hypothermia after cardiac arrest

Both pharmacological and nonpharmacological methods are used to control shivering in therapeutic hypothermia. An evidence-based protocol based on the most current research has been developed for the management of shivering during therapeutic hypothermia. Meperidine is the drug of choice and provides the greatest reduction in the shivering threshold. Other effective pharmacological agents recommended for reducing the threshold include dexmedetomidine, midazolam, fentanyl, and magnesium sulfate. In addition, skin counterwarming techniques, such as use of an air-circulating blanket, are effective nonpharmacological methods for reducing shivering when used in conjunction with medication. As a last resort, neuromuscular blocking agents are considered appropriate therapy for management of refractory shivering.     

A review of anti-inflammatory strategies in cardiac surgery

It is generally accepted that cardiac surgery is frequently associated with the development of systemic inflammatory response. This phenomenon is very variable clinically, and can be detected by measuring plasma concentrations of certain inflammatory markers. Complement component, cytokines and adhesion molecules are examples of these markers. Systemic inflammation can be potentially damaging to major organs. Several anti-inflammatory strategies have been used in recent years, aiming to attenuate the development of systemic inflammatory response. This article summarizes recently published literature concerning the use of anti-inflammatory techniques and pharmacological agents in cardiac surgery. In particular, the anti-inflammatory effects of off-pump surgery, leukocyte filtration, corticosteroids, aprotinin, phosphodiesterase inhibitors, dpoexamine, H2 antagonists and ACE inhibitors are reviewed. The overall conclusion is that although certain strategies reduce plasma levels of inflammatory mediators, convincing evidence of significant clinical benefits is yet to come.     

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery

OBJECTIVE: To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. DATA EXTRACTION: The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. DATA SYNTHESIS: Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. CONCLUSIONS: Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.     

Mechanical ventilation during extracorporeal membrane oxygenation

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.     

Recent advances in treatment and the future problems to be solved

The goal of the treatment of chronic heart failure is improvement of patient's prognosis and QOL. To achieve this goal, new pharmacological and nonpharmacological approaches have been developed. ACE inhibitor - and beta-blocker-treatment added to the standard therapy has been established to improve the prognosis, and ICD, cardiac resynchronization treatment (CRT) with biventricular pacing and LV assist device also contribute to the advances in the therapeutic progress. However, recent clinical trials for the new drugs which antagonize the endothelin receptors and TNF receptors failed to demonstrate the benefit of these new drugs. Establishment of the therapeutic strategies for treatment of diastolic heart failure is also another problem to be solved.     

Intervention strategies for neonatal hypoxic-ischemic cerebral injury

BACKGROUND: Accumulating evidence points to an evolving process of brain injury after intrapartum hypoxia-ischemia that initiates in utero and extends into a recovery period. It is during this recovery period that the potential for neuroprotection exists. OBJECTIVE: This discussion briefly reviews the cellular characteristics of hypoxic-ischemic cerebral injury and the current and future therapeutic strategies aimed at ameliorating ongoing brain injury after intrapartum hypoxia-ischemia. METHODS: As part of the Newborn Drug Development Initiative, the National Institute of Child Health and Human Development and the US Food and Drug Administration cosponsored a workshop held March 29 and 30, 2004, in Baltimore, Maryland. Information for this article was gathered during that workshop. Literature searches of MEDLINE (Ovid) and EMBASE (1996-2005) were also conducted; search terms included newborn, infant, hypoxia-ischemia, hypoxic-ischemic encephalopathy, asphyxia, pathogenesis, treatment, reperfusion injury, and mechanisms, as well as numerous interventions (ie, therapeutic hypothermia, magnesium, and barbiturates). RESULTS: The acute brain injury results from the combined effects of cellular energy failure, acidosis, glutamate release, intracellular calcium accumulation, lipid peroxidation, and nitric oxide neurotoxicity that serve to disrupt essential components of the cell, resulting in death. Many factors, including the duration or severity of the insult, influence the progression of cellular injury after hypoxia-ischemia. A secondary cerebral energy failure occurs from 6 to 48 hours after the primary event and may involve mitochondrial dysfunction secondary to extended reactions from primary insults (eg, calcium influx, excitatory neurotoxicity, oxygen free radicals, or nitric oxide formation). Some evidence suggests that circulatory and endogenous inflammatory cells/mediators also contribute to ongoing brain injury. The goals of management of a newborn infant who has sustained a hypoxic-ischemic insult and is at risk for injury should include early identification of the infant at highest risk for evolving injury, supportive care to facilitate adequate perfusion and nutrients to the brain, attempts to maintain glucose homeostasis, and consideration of interventions to ameliorate the processes of ongoing brain injury. Recent evidence suggests a potential role for modest hypothermia (ie, a reduction in core body temperature to -34 degrees C) administered to high-risk term infants within 6 hours of birth. Either selective (head) or systemic (body) cooling reduces the incidence of death and/or moderate to severe disability at 18-month follow-up. Additional strategies-including the use of oxygen free radical inhibitors and scavengers, excitatory amino acid antagonists, and growth factors; prevention of nitric oxide formation; and blockage of apoptotic pathways-have been evaluated experimentally but have not been replicated in a systematic manner in the human neonate. Other avenues of potential neuroprotection that have been studied in immature animals include platelet-activating factor antagonists, adenosinergic agents, monosialoganglioside GM1, insulin-like growth factor-1, and erythropoietin. CONCLUSIONS: Much progress has been made toward understanding the mechanisms contributing to ongoing brain injury after intrapartum hypoxia-ischemia. This should facilitate more specific pharmacologic intervention strategies that might provide neuroprotection during the reperfusion phase of injury.     

Automatic Atrial and Junctional Tachycardias in the Pediatric Patient: Strategies for Diagnosis and Management

Unlike supraventricular arrhythmias secondary to reentry, automatic rhylhm disturbances in children are rare and more resislant to standard pharmacological therapy. This article reviews strategies for the diagnosis and managemenl of two of the more common pediatric auto-matic rhylhm disliirbances, that is, atrial ectopic tachycardia, and junlional ectopic tachycardia. The place of nevver nonpharmacological therapy, such as catheter ablation, in the treatment of these entities is beginning to be explored, yet has not been fully delineated. Despite these iimitalions, there is enough experience ivith these difficult tachycardias in the pediatric age group to formulate some strategies for optimal diagnosis and management.     

Preventive neuroprotection: from experimental data to therapeutic strategies

The concept of preventive neuroprotection is based on experimental concept of brain ischemic tolerance in which a cerebral resistance against ischemia consequences is induced prior to its occurrence. Pharmacological agents mimicking the biological mechanisms observed in brain ischemic tolerance might increase the resistance of patients with high stroke risk to the deleterious effects of brain ischemia. Activation of cytoprotective proteins or regulation of deleterious molecular pathways could constitute the main pharmacological targets to induce preventive neuroprotection. Several pharmacological agents such as statins or fibrates have been demonstrated experimentally to induce a preventive neuroprotection related to their ple?otropic anti-inflammatory and antioxidant properties. In future, the prevention treatment of stroke occurrence may be completed by preventive neuroprotective treatment. Moreover, some drugs could have potentially both preventive and neuroprotective properties, which are likely linked.     

Non-pharmacological treatment of hypertension.

This paper represents a compilation of the latest scientific research on the non-pharmacological management of hypertension to help practitioners manage this highly prevalent disease. In this regard, recent evidence suggests that nonpharmacological approaches--particularly weight reduction, salt restriction, moderation of alcohol consumption, reduction of cholesterol intake and exercise--may lower elevated pressure and improve the efficacy of pharmacological agents. Non-pharmacological therapy should be stressed for the future treatment of hypertension.     

Mechanisms of cerebral injury from cardiac surgery

Cerebral injury is a frequent complication of cardiac surgery, and it has been associated with high mortality, morbidity, hospital costs; an increased likelihood of admission to a secondary care facility after hospital discharge; and impaired quality of life. This article examines postulated mechanisms for cerebral injury from cardiac surgery. Most emphasis has been placed in the past on the intraoperative interval as being the period of highest cerebral vulnerability. Many clinical cerebral events, however, occur in the postoperative period.     

Emergency management of agitation in schizophrenia

Schizophrenia is a common psychiatric condition, affecting approximately 1% of the population. Acute emergent presentations often include hallucinations, delusions, thought, and speech disorders. Agitation is common among emergency patients with schizophrenia. Decisional capacity should be assessed in all patients. Reversible causes of agitation should be ruled out, including infection, metabolic disorders, endocrine disorders, trauma, pain, noncompliance, toxicological disorders, and structural brain abnormalities. Agitation may be managed acutely using a combination of pharmacological agents and nonpharmacological interventions. Effective pharmacological agents include several classes of antipsychotic agents and benzodiazepines. Potential life-threatening complications of pharmacological therapy should be anticipated, which may include neuroleptic malignant syndrome (NMS), prolonged QT syndrome, and respiratory depression. Nonpharmacological interventions may include a quiet environment, physical restraints, and behavioral interventions. Disposition decisions should be made based on the etiology of agitation, effective management, decisional capacity, and presence of suicidal or homicidal intentions. Many patients who have required nonpharmacological or pharmacological management of agitation require inpatient psychiatric treatment, either voluntarily or involuntarily. Psychiatric consultation should be sought for patients with schizophrenia and uncertain disposition determinations, or those requiring other complex management decisions.     

Clinical treatments for mitochondrial dysfunctions after brain injury

PURPOSE OF REVIEW: This review provides a comprehensive look at the evidence supporting the role of mitochondrial dysfunction in promoting neuronal death after acute brain injury, and critically discusses the most recent proposed therapies that could limit the deleterious effects of such a dysfunction on neurological outcome. RECENT FINDINGS: Following acute brain injury, disruption of calcium homeostasis, overproduction of reactive oxygen species, and opening of the mitochondrial permeability transition pore, are key factors in promoting mitochondrial dysfunction, with ensuing activation of either necrotic or apoptotic cell death pathways. Growing interest has been focused on developing new therapeutic strategies able to oppose these mechanisms. Several pharmacological agents are currently under investigation, including novel calcium channel blockers and antioxidants, uncoupling proteins and mitochondrial permeability transition pore inhibitors. Although a 'magic bullet' has not yet been identified, the results of both preclinical and clinical studies are encouraging. SUMMARY: Therapeutic interventions directly targeting processes and mechanisms responsible for mitochondrial dysfunction, may offer neuroprotection in brain-injured patients. The multifactorial cause of mitochondrial dysfunction suggests, however, the need for further studies aimed at clarifying optimal dose and time for drug administration, as well as the logical combination/sequence of those approaches that may ultimately achieve improvement in neurological outcome.     

Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications

Conventional cardiovascular monitoring may not detect tissue hypoxia, and conventional cardiovascular support aiming at global hemodynamics may not restore tissue oxygenation. NIRS offers non-invasive online monitoring of tissue oxygenation in a wide range of clinical scenarios. NIRS monitoring is commonly used to measure cerebral oxygenation (rSO(2)), e.g. during cardiac surgery. In this review, we will show that tissue hypoxia occurs frequently in the perioperative setting, particularly in cardiac surgery. Therefore, measuring and obtaining adequate tissue oxygenation may prevent (postoperative) complications and may thus be cost-effective. NIRS monitoring may also be used to detect tissue hypoxia in (prehospital) emergency settings, where it has prognostic significance and enables monitoring of therapeutic interventions, particularly in patients with trauma. However, optimal therapeutic agents and strategies for augmenting tissue oxygenation have yet to be determined.     

The effect of hypothermia and hyperthermia on acute brain injury

The brain is extraordinarily susceptible to changes in temperature. Hyperthermia has been shown to exacerbate the biochemical cascade of secondary brain injury. Inversely, hypothermia limits the damaging effects of secondary brain injury. There has been a great deal of investigation regarding the detrimental effects of hyperthermia and the neuroprotection of hypothermia in animal studies. Within the last decade, clinical trials have begun to establish how the brain reacts to both temperature extremes. In the future, studies of hypothermia will continue in the quest of the optimal timing and degree of hypothermia. Hyperthermia will be examined in depth for its detrimental effects on an injured brain. Interventions for the prevention and treatment of hyperthermia will be explored. Nurses will implement cooling strategies to induce hypothermia, applying interventions to prevent complications, and they will also diagnose hyperthermia, deciding when and if to intervene pharmacologically and therapeutically. These advanced nursing actions will be guided by knowledge and understanding of available evidence. This article presents the pathophysiology of secondary brain injury and how it is affected by both hypothermia and hyperthermia. A review of the research leading up to clinical trials is explored, as well as a discussion of the future of temperature modulation for the brain injury patient. This information will help healthcare providers understand the effect that both hypothermia and hyperthermia have on the acutely injured brain.     

Mise au point sur les traitements de l’hypertension artérielle pulmonaire de l’enfant

Treatment of pediatric pulmonary arterial hypertension (PAH) has dramatically changed with the recent availability of specific oral drugs. These new treatments have been exclusively approved in PAH that should be differentiated from other causes of pulmonary hypertension particularly frequent in intensive care unit (ICU) patients. In pediatrics, data assessing efficacy and safety of these drugs do not exist in other settings than PAH. Consistently, these drugs are not recommended in persistent pulmonary hypertension of the newborn or during the postoperative course of cardiac surgery, even if routinely used. Treatment of PAH associated with congenital heart diseases represents a major concern and designing trials is challenging due to the possible benefits for children. Endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors have been approved in Europe for children use. Prostanoids including epoprostenol are largely used in the ICU, mostly by intravenous route. Specific PAH drugs may be used alone or in combination. Several trials are ongoing to test the best combination strategy with preliminary hopeful results suggesting significant improvement for the future. Creation of right-to-left shunts (atrioseptotomy and Potts’ anastomosis) as well as lung transplantation should be indicated when children’s clinical situation worsen despite optimal PAH pharmacological management.     

Intensive care for brain injury after cardiac arrest: therapeutic hypothermia and related neuroprotective strategies

Neurologic injury is the predominant cause of poor functional outcome in patients who are resuscitated from cardiac arrest. The management of these patients in the ICU can be challenging because of the paucity of effective therapies and lack of readily available diagnostic and prognostic tools. After several decades of failed pharmacologic neuroprotection trials, recent and well-designed randomized trials showed that therapeutic hypothermia is an effective neuroprotective measure in comatose survivors of cardiac arrest. Therapeutic hypothermia has been recommended by the International Liaison Committee on Resuscitation and has been incorporated in the American Heart Association CPR Guidelines. The American Academy of Neurology recently enhanced the delivery of care in survivors of cardiac arrest by providing evidence-based practice parameters on the prediction of poor outcome in comatose survivors of cardiac arrest, based on clinical evaluation and diagnostic tests. This article discusses these advances and their potential impact on the care provided in the ICU.