Microcirculatory effects of norepinephrine in patients with septic shock: a microdialysis study

Background: The management of septic shock requires the administration of an alpha-adrenergic drug such as norepinephrine, after optimization of the patient’s preload, to maintain adequate mean arterial pressure. Nevertheless, with optimal macrocirculatory parameters, alterations of tissue perfusion can occur. This study aimed to investigate the effect of norepinephrine dosage on microcirculation parameters, studied by microdialysis, in patients with septic shock. Methods: We conducted a retrospective study. We included all patients aged over 16 years in septic shock. We studied three groups (levosimendan, dobutamine, and control group). We administrated norepinephrine before inclusion, at stable flow for more than an hour. We performed hemodynamic monitoring of macrocirculation by echocardiography. We analyzed microcirculation parameters (lactate, pyruvate, and lactate/pyruvate ratio) every six hours during the first three days, by muscle microdialysis (CMA 600, CMA microdialysis AB, Stockholm, Sweden). We studied correlations between microcirculation parameters and norepinephrine doses.Results: We included thirty patients in the study (ten patients in each group). Demographic characteristics and mortality were comparable across the three groups. In total, we analyzed 390 samples of interstitial muscle fluid. We did not find any correlation between norepinephrine doses and the lactate concentration in the muscle, as well as the ratio of lactate/ pyruvate concentration in the muscle (p > 0.05) for all groups. We found a weak inverse correlation between norepinephrine doses and muscle pyruvate levels (p < 0.05) for the dobutamine group and the control group and but not for the levosimendan group.Conclusions: Noradrenaline dose has little effect on microcirculation when administered for hemodynamic optimization, as recommended by the Surviving Sepsis Campaign.

Cyclomydril® eye drops: An unusual contributing factor to postoperative apnoea in a neonate – A case report

Premature neonates presenting for surgery are at risk for postoperative apnoeas for various reasons, including their immature physiology, general anaesthesia, opiates and other drugs administered during a procedure. An ex-premature baby presented for a laparotomy following a complication of necrotising enterocolitis (NEC) at 39 weeks postconceptual age. An opthalmological procedure was planned to follow the laparotomy under general anaesthetic. Postoperatively the neonate remained apnoeic and the anaesthetists were unable to safely extubate her. She required ventilation in the intensive care unit (ICU) overnight. After considering all causes of postoperative apnoea in this neonate, an overdose of Cyclomydril® eye drops was thought to be a significant contributing factor. Cyclomydril® eye drops consist of cyclopentolate, an anticholinergic, and phenylephrine, an adrenergic drug. The combination produces mydriasis of short duration that is superior to that of either drug alone at the same concentration, with little or no cycloplegia. Infants are especially sensitive to cardiopulmonary and neurological side-effects of cyclopentolate due to their immature cardiovascular and neurological systems, and their immature metabolic pathways. Although very rare, Cyclomydril® drops have been known to cause apnoea, and even hypoxic arrest, in outpatient ophthalmology clinics at routine screening for retinopathy of prematurity. Anaesthetists should be aware of the potential dangers of Cyclomydril® drops and plan accordingly. It is the authors’ recommendation that neonates receiving Cyclomydril® during the course of a procedure should be admitted to a high care unit or ICU for 24 hours postoperatively for observation and apnoea monitoring.

Cyclomydril® eye drops: An unusual contributing factor to postoperative apnoea in a neonate – A case report

Premature neonates presenting for surgery are at risk for postoperative apnoeas for various reasons, including their immature physiology, general anaesthesia, opiates and other drugs administered during a procedure. An ex-premature baby presented for a laparotomy following a complication of necrotising enterocolitis (NEC) at 39 weeks postconceptual age. An opthalmological procedure was planned to follow the laparotomy under general anaesthetic. Postoperatively the neonate remained apnoeic and the anaesthetists were unable to safely extubate her. She required ventilation in the intensive care unit (ICU) overnight. After considering all causes of postoperative apnoea in this neonate, an overdose of Cyclomydril® eye drops was thought to be a significant contributing factor. Cyclomydril® eye drops consist of cyclopentolate, an anticholinergic, and phenylephrine, an adrenergic drug. The combination produces mydriasis of short duration that is superior to that of either drug alone at the same concentration, with little or no cycloplegia. Infants are especially sensitive to cardiopulmonary and neurological side-effects of cyclopentolate due to their immature cardiovascular and neurological systems, and their immature metabolic pathways. Although very rare, Cyclomydril® drops have been known to cause apnoea, and even hypoxic arrest, in outpatient ophthalmology clinics at routine screening for retinopathy of prematurity. Anaesthetists should be aware of the potential dangers of Cyclomydril® drops and plan accordingly. It is the authors’ recommendation that neonates receiving Cyclomydril® during the course of a procedure should be admitted to a high care unit or ICU for 24 hours postoperatively for observation and apnoea monitoring.

197 Guanfacine and Impulsivity – Review of Literature

Prefrontal cortex (PFC) represents one of the most evolved regions of primate brain that is thought to regulate human specific features such as cognition, emotion and behavior (Arnsten and Jin, 2012). PFC is a site of action of guanfacine, an agonist of alpha 2 adrenergic receptors. Compared to clonidine, another alpha adrenergic drug, guanfacine is more selective for α2A adrenergic receptor subtype (van Zwieten et al., 1994; Uhlen at al., 1995) and is weaker in producing hypotension andsedation (Jurado at al., 1998) resulting in better tolerability of the medication. Studies have shown that endogenous noradrenergic stimulation of alpha2A receptors is essential for PFC regulation of behavior, thought and emotion as blockade ofα2A receptors in the monkey dorsolateral PFC significantly impairs working memory (Li and Mei, 1994) and behavioral inhibition (Ma et al., 2003; Ma et al., 2003). So far FDA has approved guanfacine in treatment of attention deficit hyperactivity disorder in children but the medication is used off label for treatment of oppositional defiant disorder, conduct disorder, pervasive developmental disorders, motor tics and Tourette’s syndrome as well. Impulsivity as used in clinical terms is very broadly defined and encompasses personality traits as well as cognitive functions such as emotion regulation and behavioral inhibition. Numerous studies have shown effectiveness of extended release guanfacine in reducing impulsiveness in children with ADHD and recently in autism spectrum disorder (Scahill et al., 2015), however limited data is available on use of guanfacine in treatment of impulse control and aggression in adults.Funding AcknowledgementsNo funding.

Phenylephrine-induced epistaxis in a six-year-old Quarter horse with nephrosplenic entrapment

Left dorsal displacement of the large colon is a common cause of colic in horses. Treatment consists of surgery, rolling the horse under general anesthesia or intravenous administration of phenylephrine. Treatment with phenylephrine, an α1-adrenergic drug, is often associated with sweating and trembling. Especially in horses of more than 15 years old, fatal hemorrhage may occur due to hemothorax or hemoperitoneum. Therefore, phenylephrine treatment is generally not given in horses over 15 years of age. In this report, severe epistaxis in a six-year-old Quarter horse is described after intravenous administration of 22.5 μg/kg BW phenylephrine, and it is highlighted that hemorrhage may also occur in younger horses.