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Background: Children undergoing cleft palate repair present challenges to postoperative management due to several factors that can complicate recovery. Utilization of multimodal analgesic protocols can improve outcomes in this population. We report experience designing and implementing an enhanced recovery after surgery (ERAS) pathway for cleft palate repair to optimize postoperative recovery. Aims: The primary aim was to implement an ERAS pathway with >70% bundle adherence to achieve a 30% reduction in postoperative opioid consumption within 12 months. Our secondary aims assessed intraoperative opioid consumption, length of stay, timeliness of oral intake, and respiratory recovery. Methods: A multidisciplinary team of perioperative providers developed an ERAS pathway for cleft palate patients. Key drivers included patient and provider education, formal pathway creation and implementation, multimodal pain therapy, and target‐based care. Interventions included maxillary nerve blockade and enhanced intra‐ and postoperative medication regimens. Outcomes were displayed as statistical process control charts. Results: Pathway compliance was 77.0%. Patients during the intervention period (n = 39) experienced a 49% reduction in postoperative opioid consumption (p <.0001) relative to our historical cohort (n = 63), with a mean difference of −0.33 ± 0.11 mg/kg (95% CI −0.55 to −0.12 mg/kg). Intraoperative opioid consumption was reduced by 36% (p =.002), with a mean difference of −0.27 ± 0.09 mg/kg (95% CI −0.45 to −0.09 mg/kg). Additionally, patients in the intervention group had a 45% reduction in time to first oral intake (p =.02) relative to our historical cohort, with a mean difference of −3.81 ± 1.56 h (95% CI −6.9 to −0.70). There was no difference in PACU or hospital length of stay, but there was a significant reduction in variance of all secondary outcomes. Conclusion: Opioid reduction and improved timeliness of oral intake is possible with an ERAS protocol for cleft palate repair, but our protocol did not alter PACU or hospital length of stay. [ABSTRACT FROM AUTHOR]

6-hydroxydopamine (6-OHDA) is used to "chemically denervate" tissues innervated by nerves containing catecholamine transporters. Treatment reduces the norepinephrine (NE) content of the heart but little is known about other markers of sympathetic nerves. The purpose of this study was to examine the effects of 6-OHDA on cardiac sympathetic neurons innervating the right atrium. 6-OHDA (250 mg/kg, sub.q, 3 doses over 7 days) was administered to adult rats and on day 7 hearts were removed. There was a significant decrease in NE levels determined by capillary electrophoresis with electrochemical detection (p<0.001, n=3) confirming that the treatment was effective. However, immunocytochemical staining showed tyrosine hydroxylase was still visible in neurons after denervation (n=3). Western blotting revealed no differences in protein expression for either the neuronal marker Protein Gene Product 9.5 (p>0.05, n=4) or for three molecular weight variants of NE transporter (NET) (80, 54, and 46 kD) in the right atria (p>0.05. n=3-4). In addition, qPCR showed no change in the levels of mRNA for NET compared to untreated controls (p>0.05, n=6). Similar results were seen in all other heart chambers. Therefore, 6-OHDA does not destroy cardiac sympathetic nerve fibers; its action appears limited to the depletion of NE. [ABSTRACT FROM AUTHOR]

Abstract: Uptake of norepinephrine via the neuronal norepinephrine transporter is reduced in the heart during deoxycorticosterone (DOCA)–salt hypertension. We hypothesized that this was due to reduced norepinephrine transporter mRNA and/or protein expression in the stellate ganglia and heart. After 4weeks of DOCA–salt treatment there was no change in norepinephrine transporter mRNA in either the right or the left stellate ganglia from hypertensive rats (n=5–7, p>0.05). Norepinephrine transporter immunoreactivity in the left stellate ganglion was significantly increased (n=4, p<0.05) while the right stellate ganglion was unchanged (n=4, p>0.05). Whole heart norepinephrine content was significantly reduced in DOCA rats consistent with reduced uptake function; however, when norepinephrine was assessed by chamber, a significant decrease was noted only in the right atrium and right ventricle (n=6, p<0.05). Cardiac norepinephrine transport binding by chamber revealed that it was only reduced in the left atrium (n=5–7, p>0.05). Therefore, 1) contrary to our hypothesis reduced reuptake in the hypertensive heart is not exclusively due to an overall reduction in norepinephrine transporter mRNA or protein in the stellate ganglion or heart, and 2) norepinephrine transporter regulation occurs regionally in the heart and stellate ganglion in the hypertensive rat heart. [Copyright &y& Elsevier]

Cardiac sympathetic innervation originates in the stellate ganglia. Norepinephrine (NE) reuptake via NE transporter (NET), and release of NE from sympathetic nerve terminals are regulated by the endothelin-I (ET1) receptors, ETA and ETB, respectively. Regulation of NET by ET1 in the stellate ganglia is unknown. ETB receptor deficient rats (ETB -/-) lack functional ETB receptors in all tissues except those expressing dopamine beta hyrdoxylase (DBH). Since functional ETB expression is coupled to DBH promoter (DBH-ETB) in this model, it is possible that sympathetic neurons overexpress ETB. The purpose of this study was to examine ETB and NET in the stellate ganglia of ETB -/- rats using histology and PCR. Histology revealed that there was a significant elevation of ETB receptor protein in both the nuclear (n=4, p<0.0001) and cytoplasmic compartments (n=4, p<0.0001) in bilateral stellate ganglia from ETB -/- rats. In all stellate ganglion neurons from ETB -/- rats, NET protein was significantly increased (n=3, p<0.05), while NET mRNA was unchanged (n=3-6, p>0.05), suggesting that ET1 modulation of NET is post-transcriptional. In summary, the ETB -/- rat overexpresses ETB and NET protein in the stellate ganglia revealing an important feature of this animal model that is otherwise devoid of functional ETB receptors. This supports the notion that altered ET1 signaling can regulate NET in ganglia. [ABSTRACT FROM AUTHOR]

Reduced norepinephrine (NE) reuptake and NE transporter (NET) in the heart are associated with hypertension. Sympathetic neurons in the stellate ganglia innervate the heart and direct nearly all cardiac sympathetic activity. The purpose of this study was to compare the regulation of NET in bilateral stellate ganglia of normotensive and hypertensive rats (DOCA-salt). Total RNA was isolated from ganglia and RT-qPCR was performed to analyze NET mRNA levels. NET mRNA levels were 4.48 fold higher in hypertensive left stellate than in normotensive left stellate (p=.13, n=6-7). NET mRNA in the right stellate was unchanged with hypertension (p>.05, n=7-10). Additional ganglia were fixed and sectioned for immunohistochemistry with a NET antibody against a cytoplasmic loop of the protein. All neurons in both ganglia were immunoreative for NET. Staining for NET in left stellate neurons from hypertensive animals was significantly more intense than normotensive (p<0.05, n=4). NET staining intensity in right stellate neurons was not different in hypertension (p>0.05, n=4). Increased NET mRNA and protein levels in the left stellate ganglia may serve as a compensatory mechanism when NET function is reduced in the heart during hypertension. This study indicates separate regulatory control of NET between right and left stellate, and also between nerve cell bodies and terminals. [ABSTRACT FROM AUTHOR]