Sympathetic hyperactivity, respiratory failure, pruritus, and anesthesia after unintentional epidural injection of potassium chloride: Case report

Background and Objectives. A combination of epidural and general anesthesia has been widely used to attenuate the surgical stress response and to provide postoperative analgesia. This case report illustrates the use of this anesthetic technique. Analgesia was induced with local anesthetic in the immediate postoperative period using unintentional 19.1% potassium chloride (KCI) as diluent. Methods. An ASA I male patient was scheduled for surgical correction of idiopathic megaesophagus under continuous epidural anesthesia combined with general anesthesia. In the postoperative period, while preparing 10 mt 0.125% bupivacaine to be administered through the epidural catheter for pain control, 5 mt 19.1% KCI was unintentionally used as diluent, resulting in a 9.55% potassium solution concentration. Results. The patient developed warmness of the lower limbs, tachycardia, hypertension, intense pruritus on the chest, agitation, exacerbation of sensory and motor blocks, and respiratory failure secondary to pulmonary edema, requiring ventilatory support. Total recovery was observed after 24 hours. Conclusions. Epidurally injected potassium leads to severe clinical manifestations caused by autonomic dysfunction, spinal cord irritation, and possible release of histamine. Despite continuous recommendations, ampule misidentification still happens in hospitals, frequently leading to serious accidents.

Reconsiderations about the clinical importance of the sympathetic skin response

Over the last few years, neurologists have been showing increasing interest in the study of the sympathetic skin response (SSR). In the present report we describe a simple method that permitted us to determine a wide variation of SSR in response to different stimuli such as respiration, deglutition, blinking, skeletal movements, biting, auditory or light stimuli, vocalization, and sphincter contraction. These results raise doubts about the role of SSR as a complementary diagnostic method.

Differential effects of variation in athletes training on myocardial morphophysiological adaptation in men: Focus on I-123-MIBG assessed myocardial sympathetic activity

High intensity systematic physical training leads to myocardial morphophysiological adaptations. The goal of this study was to investigate if differences in training were correlated with differences in cardiac sympathetic activity.58 males (19-47 years), were divided into three groups: strength group (SG), (20 bodybuilders), endurance group (EG), (20 endurance athletes), and a control group (CG) comprising 18 healthy non-athletes. Cardiac sympathetic innervation was assessed by planar myocardial I-123-metaiodobenzylguanidine scintigraphy using the early and late heart to mediastinal (H/M) ratio, and washout rate (WR).Left ventricular mass index was significantly higher both in SG (P < .001) and EG (P = .001) compared to CG without a statistical significant difference between SG and EG (P = .417). The relative wall thickness was significantly higher in SG compared to CG (P < .001). Both left ventricular ejection fraction and the peak filling rate showed no significant difference between the groups. Resting heart rate was significantly lower in EG compared to CG (P = .006) and SG (P = .002). The late H/M ratio in CG was significantly higher compared to the late H/M for SG (P = .003) and EG (P = .004). However, WR showed no difference between the groups. There was no significant correlation between the parameters of myocardial sympathetic innervation and parameters of left ventricular function.Strength training resulted in a significant increase in cardiac dimensions. Both strength and endurance training seem to cause a reduction in myocardial sympathetic drive. However, myocardial morphological and functional adaptations to training were not correlated with myocardial sympathetic activity.

Differential modulation of sympathetic and respiratory activities by cholinergic mechanisms in the nucleus of the solitary tract in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Short-term sustained hypoxia induces changes in the coupling of sympathetic and respiratory activities in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The nucleus of the solitary tract and the coordination of respiratory and sympathetic activities

It is well known that breathing introduces rhythmical oscillations in the heart rate and arterial pressure levels. Sympathetic oscillations coupled to the respiratory activity have been suggested as an important homeostatic mechanism optimizing tissue perfusion and blood gas uptake/delivery. This respiratory-sympathetic coupling is strengthened in conditions of blood gas challenges (hypoxia and hypercapnia) as a result of the synchronized activation of brainstem respiratory and sympathetic neurons, culminating with the emergence of entrained cardiovascular and respiratory reflex responses. Studies have proposed that the ventrolateral region of the medulla oblongata is a major site of synaptic interaction between respiratory and sympathetic neurons. However, other brainstem regions also play a relevant role in the patterning of respiratory and sympathetic motor outputs. Recent findings suggest that the neurons of the nucleus of the solitary tract (NTS), in the dorsal medulla, are essential for the processing and coordination of respiratory and sympathetic responses to hypoxia. The NTS is the first synaptic station of the cardiorespiratory afferent inputs, including peripheral chemoreceptors, baroreceptors and pulmonary stretch receptors. The synaptic profile of the NTS neurons receiving the excitatory drive from afferent inputs is complex and involves distinct neurotransmitters, including glutamate, ATP and acetylcholine. In the present review we discuss the role of the NTS circuitry in coordinating sympathetic and respiratory reflex responses. We also analyze the neuroplasticity of NTS neurons and their contribution for the development of cardiorespiratory dysfunctions, as observed in neurogenic hypertension, obstructive sleep apnea and metabolic disorders.

Contribution of retrotrapezoid/parafacial respiratory region to the expiratory-sympathetic coupling in response to peripheral chemoreflex in rats

Central mechanisms of coupling between respiratory and sympathetic systems are essential for the entrainment between the enhanced respiratory drive and sympathoexcitation in response to hypoxia. However, the brainstem nuclei and neuronal network involved in these respiratory-sympathetic interactions remain unclear. Here, we evaluated whether the increase in expiratory activity and expiratory-modulated sympathoexcitation produced by the peripheral chemoreflex activation involves the retrotrapezoid nucleus/parafacial respiratory region (RTN/pFRG). Using decerebrated arterially perfused in situ rat preparations (60–80 g), we recorded the activities of thoracic sympathetic (tSN), phrenic (PN), and abdominal nerves (AbN) as well as the extracellular activity of RTN/pFRG expiratory neurons, and reflex responses to chemoreflex activation were evaluated before and after inactivation of the RTN/pFRG region with muscimol (1 mM). In the RTN/pFRG, we identified late-expiratory (late-E) neurons (n = 5) that were silent at resting but fired coincidently with the emergence of late-E bursts in AbN after peripheral chemoreceptor activation. Bilateral muscimol microinjections into the RTN/pFRG region (n = 6) significantly reduced basal PN frequency, mean AbN activity, and the amplitude of respiratory modulation of tSN (P < 0.05). With respect to peripheral chemoreflex responses, muscimol microinjections in the RTN/pFRG enhanced the PN inspiratory response, abolished the evoked late-E activity of AbN, but did not alter either the magnitude or pattern of the tSN reflex response. These findings indicate that the RTN/pFRG region is critically involved in the processing of the active expiratory response but not of the expiratory-modulated sympathetic response to peripheral chemoreflex activation of rat in situ preparations.

Glutamatergic antagonism in the NTS decreases post-inspiratory drive and changes phrenic and sympathetic coupling during chemoreflex activation

For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coupling of respiratory and sympathetic activities in rats submitted to chronic intermittent hypoxia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of acute intermittent hypoxia on sympathetic and expiratory activities in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats

The aim of the present study was to investigate the participation of the sympathetic nervous system (SNS) in the control of glycerol-3-P (G3P) generating pathways in white adipose tissue (WAT) of rats in three situations in which the plasma insulin levels are low. WAT from 48 h fasted animals, 3 day-streptozotocin diabetic animals and high-protein, carbohydrate-free (HP) diet-fed rats was surgical denervated and the G3P generation pathways were evaluated. Food deprivation, diabetes and the HP diet provoke a marked decrease in the rate of glucose uptake and glycerokinase (GyK) activity, but a significant increase in the glyceroneogenesis, estimated by the phosphoenolpyruvate carboxykinase (PEPCK) activity and the incorporation of 1-[C-14]-pyruvate into glycerol-TAG. The denervation provokes a reduction (similar to 70%) in the NE content of WAT in fasted, diabetic and HP diet-fed rats. The denervation induced an increase in WAT glucose uptake of fed, fasted, diabetic and HP diet-fed rats (40%, 60%, 3.2 fold and 35%, respectively). TAG-glycerol synthesis from pyruvate was reduced by denervation in adipocytes of fed (58%) and fasted (36%), saline-treated (58%) and diabetic (23%), and HP diet-fed rats (11%). In these same groups the denervation reduced the PEPCK mRNA expression (75%-95%) and the PEPCK activity (35%-60%). The denervation caused a similar to 35% decrease in GyK activity of control rats and a further similar to 35% reduction in the already low enzyme activity of fasted, diabetic and HP diet-fed rats. These data suggest that the SNS plays an important role in modulating G3P generating pathways in WAT, in situations where insulin levels are low. (C) 2012 Elsevier Inc. All rights reserved.

Left cardiac sympathetic denervation for treatment of symptomatic systolic heart failure patients: a pilot study

To evaluate the feasibility, safety, and potential beneficial effects of left cardiac sympathetic denervation (LCSD) in systolic heart failure (HF) patients. In this prospective, randomized pilot study, inclusion criteria were New York Heart Association (NYHA) functional class II or III, left ventricular ejection fraction (LVEF) 40, sinus rhythm, and resting heart rate 65 b.p.m., despite optimal medical therapy (MT). Fifteen patients were randomly assigned either to MT alone or MT plus LCSD. The primary endpoint was safety, measured by mortality in the first month of follow-up and morbidity according to pre-specified criteria. Secondary endpoints were exercise capacity, quality of life, LVEF, muscle sympathetic nerve activity (MSNA), brain natriuretic peptide (BNP) levels and 24 h Holter mean heart rate before and after 6 months. We studied clinical effects in long-term follow-up. Ten patients underwent LCSD. There were no adverse events attributable to surgery. In the LCSD group, LVEF improved from 25 6.6 to 33 5.2 (P 0.03); 6 min walking distance improved from 167 35 to 198 47 m (P 0.02). Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score physical dimension changed from 21 5 to 15 7 (P 0.06). The remaining analysed variables were unchanged. During 848 549 days of follow-up, in the MT group, three patients either died or underwent cardiac transplantation (CT), while in the LCSD group six were alive without CT. LCSD was feasible and seemed to be safe in systolic HF patients. Its beneficial effects warrant the development of a larger randomized trial. Trail registration: NCT01224899.