Incorporation of the Transverse Thoracic Plane Block Into a Multimodal Early Extubation Protocol for Cardiac Surgical Patients.

BACKGROUND: The aim for early extubation remains an important goal in cardiac surgical patients. Therefore, employment of a multimodal approach to pain management that includes a transverse thoracic plane block was retrospectively examined at a single-center tertiary care hospital on the effects of time to extubation, opioid consumption, and length of stay in patients undergoing cardiac surgery via median sternotomy. METHODS: Blocks were performed on all cardiac surgical patients except for those undergoing left ventricular assist device placement, thoracic transplant, emergent surgery, or redo sternotomy. Following additional exclusions for intra- and postoperative complications unrelated to anesthesia, final analysis was conducted on 75 patients per group. Multimodal pain management included intravenous analgesics and transverse thoracic plane block where patients received 15 mL 0.5% bupivacaine + epinephrine bilaterally under ultrasound guidance prior to incision. RESULTS: Following transverse thoracic plane block and multimodal analgesics, 50.6% of patients were extubated in the operation room versus 8.6% in the control group. Intraoperative opioids were decreased, and intensive care unit and total length of stay were reduced by 5 hours and 1 day, respectively, in block patients as compared with controls. Postoperative opioids were not significantly different. There were no reported complications directly attributed to the block. CONCLUSIONS: The transverse thoracic plane block and multimodal regimen for patients undergoing median sternotomy resulted in a significant number of patients extubated in the operation room without an increase in postoperative re-intubations. Moreover, the block appears to be a quick and safe procedure to utilize on cardiac surgery patients.

Perioperative Management for Rectal Migration of a Ventriculoperitoneal Shunt.

Background: While ventriculoperitoneal shunt (VPS) is the most commonly performed surgical procedure for treating hydrocephalus, complications following shunt placement are associated with a high mortality rate. Preoperative medical optimization and surgery are the primary means of correcting shunt migration. We present the case of an 11-week-old patient who underwent emergent surgical intervention for transrectal VPS migration and associated infection. Case Report: An 11-week-old female presented with VPS tubing protruding from her rectum. The patient had a history of grade III intraventricular hemorrhage complicated by hydrocephalus status post VPS placement at age 3 weeks. Shunt tap demonstrated gross infection, and she was started prophylactically on broad-spectrum antibiotics. She was taken emergently to the operating room (OR) for VPS externalization and exploratory minilaparotomy. VPS tubing was removed, and the patient was transferred to the pediatric intensive care unit for postoperative management. Cultures confirmed methicillin-resistant Staphylococcus aureus, and the patient was treated according to infectious disease recommendations. On postoperative day (POD) 5, the patient had a full component VPS replacement. On POD 23, computed tomography scan of the head obtained for lethargy demonstrated a new midline shift, and she was returned to the OR for another VPS replacement. A small abscess was discovered and drained; postoperative cerebrospinal fluid laboratory values normalized after drainage. Once the infectious process cleared, the VPS was internalized on POD 33, and the patient was discharged home on POD 35. Conclusion: Few case reports detail the appropriate anesthetic considerations for cases of VPS migration. This report describes shunt migration pathophysiology and patient assessment with a focus on anesthetic preparation and management for this rare complication.

Opiate-Free Tricuspid Valve Replacement: Case Report.

The utility of opioid pain medications for perioperative analgesia is well described. However, opioids have many dangerous side effects including respiratory depression, acute tolerance, hyperalgesia, and chronic opioid dependence. Multimodal approaches continue to be used in more invasive and complex surgical procedures for enhanced recovery and decreased postoperative complications from opioid administration. The current case report centers on a 30-year-old male recovering from opioid addiction presenting with severe tricuspid regurgitation scheduled to undergo a tricuspid valve replacement. The patient requested an opioid-free procedure, and a multimodal plan was developed for intraoperative and postprocedure management. This case represents a completely opioid-free valve replacement surgery and recovery.

Intima-media thickness at different arterial segments in pediatric type 1 diabetes patients and its relationship with advanced glycation end products.

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) are at risk for premature atherosclerosis (AS), which has its origin in childhood. Carotid intima-media thickness (IMT) is an established surrogate marker for subclinical AS in adults. The first macroscopically detectable AS changes, however, begin in the abdominal aorta. Advanced glycation end products (AGE) predict microvascular complications in diabetes. OBJECTIVES: To assess the sensitivity for early macrovascular changes of brachial, femoral, and aortic IMT compared to conventional carotid IMT in pediatric T1DM patients ; and the relationship of IMT with AGE. METHODS: Using high-resolution external ultrasound, carotid, brachial, femoral, and aortic IMT were prospectively analyzed in children and adolescents with established T1DM and in controls (Ctrls). AGE were estimated by skin intrinsic fluorescence (SIF). Other established cardiovascular risk factors were excluded. RESULTS: Seventy-six subjects (T1DM = 38; Ctrls = 38) with a mean age of 13.1 ± 4.0 years (6-19, median 13) qualified for analysis. Carotid, brachial, femoral, and aortic IMT analyses were feasible in 100%, 74%, 84%, and 92% of subjects, respectively. Aortic and femoral IMT were increased in T1DM patients (0.60 ± 0.11 vs 0.52 ± 0.10 mm, P < .001; and 0.41 ± 0.07 vs 0.36 ± 0.07 mm, P < .01, respectively) while carotid and brachial IMT were not. AGE levels were elevated in T1DM patients and correlated with aortic IMT only. The influence of AGE on aIMT did not remain significant after adjusting for T1DM and age in our small population. CONCLUSION: We found aortic IMT-and to a lesser degree femoral IMT-to be more sensitive than carotid and brachial IMT for detecting early macrovascular changes in pediatric T1DM patients.

Clinical Case of the Month: A 49-Year-Old Man with Fever, Headache and Leg Weakness.

A 49-year-old man with an unremarkable past medical history presented to an outside hospital with a five-day history of fever, left leg weakness, myalgia and headache. The patient reported that the illness started as a fever and sore throat and he was originally diagnosed with streptococcal pharyngitis and prescribed antibiotics. The day after his initial diagnosis, his fever had progressed to include a headache, myalgia, a rash on his upper torso and right shoulder and sudden-onset left leg weakness with preserved sensation. With progressively worsening symptoms, he eventually presented to a local emergency department (ED), five days after his symptoms first started. He was experiencing continued left leg weakness, an inability to ambulate, persistent fevers to 103ºF, muscle aches, an intense band-like headache and confusion. The patient denied neck stiffness, photophobia, loss of sensation or any additional muscle weakness. He denied any recent travel aside from work, any sick contacts, recent tick/insect bites, history of sexually transmitted diseases or contact with animals. He reported no history of illicit drug use as well as no recent weight loss, trauma or radiation exposure. The patient had approximately a 10-pack-year tobacco smoking history. For the last ten years he drank about a six-pack of beer daily while onshore (roughly two weeks out of every month). He works on an offshore oil platform. He was not taking any home medications besides his recently prescribed antibiotics. He lived alone at home in a moderately rural area of South Louisiana. His family history was non-contributory.

Inhibition of TNF in the brain reverses alterations in RAS components and attenuates angiotensin II-induced hypertension.

Dysfunction of brain renin-angiotensin system (RAS) components is implicated in the development of hypertension. We previously showed that angiotensin (Ang) II-induced hypertension is mediated by increased production of proinflammatory cytokines (PIC), including tumor necrosis factor (TNF), in brain cardiovascular regulatory centers such as the paraventricular nucleus (PVN). Presently, we tested the hypothesis that central TNF blockade prevents dysregulation of brain RAS components and attenuates Ang II-induced hypertension. Male Sprague-Dawley rats were implanted with radio-telemetry transmitters to measure mean arterial pressure (MAP) and subjected to intracerebroventricular (i.c.v.) infusion of etanercept (10 µg/kg/day) with/without concurrent subcutaneous 4-week Ang II (200 ng/kg/min) infusion. Chronic Ang II infusion resulted in a significant increase in MAP and cardiac hypertrophy, which was attenuated by inhibition of brain TNF with etanercept. Etanercept treatment also attenuated Ang II-induced increases in PIC and decreases in IL-10 expression in the PVN. Additionally, Ang II infusion increased expression of pro-hypertensive RAS components (ACE and AT1R), while decreasing anti-hypertensive RAS components (ACE2, Mas, and AT2 receptors), within the PVN. I.c.v. etanercept treatment reversed these changes. Ang II-infusion was associated with increased oxidative stress as indicated by increased NAD(P)H oxidase activity and super oxide production in the PVN, which was prevented by inhibition of TNF. Moreover, brain targeted TNF blockade significantly reduced Ang II-induced NOX-2 and NOX-4 mRNA and protein expression in the PVN. These findings suggest that chronic TNF blockade in the brain protects rats against Ang II-dependent hypertension and cardiac hypertrophy by restoring the balance between pro- and anti-hypertensive RAS axes and inhibiting PIC and oxidative stress genes and proteins in the PVN.

Angiotensin II-induced hypertension is modulated by nuclear factor-κBin the paraventricular nucleus.

Hypertension is considered a low-grade inflammatory condition, and understanding the role of transcription factors in guiding this response is pertinent. A prominent transcription factor that governs inflammatory responses and has become a focal point in hypertensive research is nuclear factor-κB (NFκB). Within the hypothalamic paraventricular nucleus (PVN), a known brain cardioregulatory center, NFκB becomes potentially even more important in ultimately coordinating the systemic hypertensive response. To definitively demonstrate the role of NFκB in the neurogenic hypertensive response, we hypothesized that PVN NFκB blockade would attenuate angiotensin II-induced hypertension. Twelve-week-old male Sprague-Dawley rats were implanted with radiotelemetry probes for blood pressure measurement and allowed a 7-day recovery. After baseline blood pressure recordings, rats were administered either continuous NFκB decoy oligodeoxynucleotide infusion or microinjection of a serine mutated adenoviral inhibitory-κB vector, or their respective controls, bilaterally into the PVN to inhibit NFκB at two levels of its activation pathway. Simultaneously, rats were implanted subcutaneously with an angiotensin II or saline-filled 14-day osmotic minipump. After the 2-week treatments, rats were euthanized and brain tissues collected for PVN analysis. Bilaterally inhibited NFκB rats had a decrease in blood pressure, NFκB p65 subunit activity, proinflammatory cytokines, and reactive oxygen species, including the angiotensin II type 1 receptor, angiotensin-converting enzyme, tumor necrosis factor, and superoxide in angiotensin II-treated rats. Moreover, after NFκB blockade, key protective antihypertensive renin-angiotensin system components were upregulated. This demonstrates the important role that transcription factor NFκB plays within the PVN in modulating and perpetuating the hypertensive response via renin-angiotensin system modulation.

NF-κB in the paraventricular nucleus modulates neurotransmitters and contributes to sympathoexcitation in heart failure.

Findings from our laboratory indicate that proinflammatory cytokines and their transcription factor, nuclear factor-kappaB (NF-κB), are increased in the hypothalamic paraventricular nucleus (PVN) and contribute towards the progression of heart failure. In this study, we determined whether NF-κB activation within the PVN contributes to sympathoexcitation via interaction with neurotransmitters in the PVN during the pathogenesis of heart failure. Heart failure was induced in rats by left anterior descending coronary artery ligation. Sham-operated control (SHAM) or heart failure rats were treated for 4 weeks through bilateral PVN infusion with SN50, SN50M or vehicle via osmotic minipump. Rats with heart failure treated with PVN vehicle or SN50M (inactive peptide for SN50) had increased levels of glutamate, norepinephrine (NE), tyrosine hydroxylase (TH), superoxide, gp91(phox) (a subunit of NAD(P)H oxidase), phosphorylated IKKß and NF-κB p65 activity, and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN compared with those of SHAM rats. Plasma levels of cytokines, norepinephrine, epinephrine and angiotensin II, and renal sympathetic nerve activity (RSNA) were increased in heart failure rats. Bilateral PVN infusion of SN50 prevented the decreases in PVN GABA and GAD67, and the increases in RSNA and PVN glutamate, norepinephrine, TH, superoxide, gp91(phox), phosphorylated IKKß and NF-κB p65 activity observed in vehicle or SN50M-treated heart failure rats. A same dose of SN50 given intraperitoneally did not affect neurotransmitters concentration in the PVN and was similar to vehicle-treated heart failure rats. These findings suggest that NF-κB activation in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced heart failure.

ACE2 overexpression in the paraventricular nucleus attenuates angiotensin II-induced hypertension.

AIMS: Angiotensin II (Ang II) has been shown to have both central and peripheral effects in mediating hypertension, for which the hypothalamic paraventricular nucleus (PVN) is an important brain cardio-regulatory centre. Angiotensin-converting enzyme 2 (ACE2) has been identified as a negative regulator of the pro-hypertensive actions of Ang II. Recent findings from our laboratory suggest that Ang II infusion decreases ACE2 expression in the PVN. In the present study, we hypothesized that ACE2 overexpression in the PVN will have beneficial effects in counteracting Ang II-induced hypertension. METHODS AND RESULTS: Male Sprague-Dawley rats were used in this study. Bilateral microinjection of an adenovirus encoding hACE2 (Ad-ACE2) into the PVN was used to overexpress ACE2 within this region. Mean arterial pressure measured by radiotelemetry was significantly increased after 14 days in Ang II-infused (200 ng/kg/min) rats vs. saline-infused controls (162.9 ± 3.6 vs. 102.3 ± 1.5 mmHg). Bilateral PVN microinjection of Ad-ACE2 attenuated this Ang II-induced hypertension (130.2 ± 5.7 vs. 162.9 ± 3.6 mmHg). ACE2 overexpression also significantly decreased AT(1)R and ACE expression and increased AT(2)R and Mas expression in the PVN. Additionally, ACE2 overexpression in the PVN attenuated the Ang II-induced increase in the expression of the pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-1ß and IL-6 in the PVN. CONCLUSION: Our findings suggest that attenuation of pro-inflammatory cytokines in the PVN in combination with the shift of the renin-angiotensin system towards the anti-hypertensive axis (ACE2/Ang-(1-7)/Mas) may be responsible for the overall beneficial effects of ACE2 overexpression in the PVN on the Ang II-induced hypertensive response.

Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure.

Recent studies indicate that systemic administration of tumor necrosis factor (TNF)-α induces increases in corticotrophin releasing hormone (CRH) and CRH type 1 receptors in the hypothalamic paraventricular nucleus (PVN). In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague-Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the increases in RSNA, ACTH and PVN glutamate, NE and TH observed in HF rats. These findings suggest that CRH in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced HF.

Central TNF inhibition results in attenuated neurohumoral excitation in heart failure: a role for superoxide and nitric oxide.

This study examined the effect of central tumor necrosis factor-alpha (TNF) blockade on the imbalance between nitric oxide and superoxide production in the paraventricular nucleus (PVN) and ventrolateral medulla (VLM), key autonomic regulators, and their contribution to enhanced sympathetic drive in mice with congestive heart failure (CHF). We also used a TNF gene knockout (KO) mouse model to study the involvement of TNF in body fluid homeostasis and sympathoexcitation in CHF. After implantation of intracerebroventricular (ICV) cannulae, myocardial infarction (MI) was induced in wild-type (WT) and KO mice by coronary artery ligation. Osmotic mini-pumps were implanted into one set of WT + MI/Sham mice for continuous ICV infusion of Etanercept (ETN), a TNF receptor fusion protein, or vehicle (VEH). Gene expressions of neuronal nitric oxide synthase (NOS) and angiotensin receptor-type 2 were reduced, while those of inducible NOS, Nox2 homologs, superoxide, peroxynitrite and angiotensin receptor-type 1 were elevated in the brainstem and hypothalamus of MI + VEH. Plasma norepinephrine levels and the number of Fos-positive neurons were also increased in the PVN and VLM in MI + VEH. MI + ETN and KO + MI mice exhibited reduced oxidative stress, reduced sympathoexcitation and an improved cardiac function. These changes in WT + MI were associated with increased sodium and fluid retention. These results indicate that elevated TNF in these autonomic regulatory regions of the brain alter the production of superoxide and nitric oxide, contributing to fluid imbalance and sympathoexcitation in CHF.

HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats.

Reactive oxygen species and proinflammatory cytokines contribute to cardiovascular diseases. Inhibition of downstream transcription factors and gene modifiers of these components are key mediators of hypertensive response. Histone acetylases/deacetylases can modulate the gene expression of these hypertrophic and hypertensive components. Therefore, we hypothesized that long-term inhibition of histone deacetylase with valproic acid might attenuate hypertrophic and hypertensive responses by modulating reactive oxygen species and proinflammatory cytokines in SHR rats. Seven-week-old SHR and WKY rats were used in this study. Following baseline blood pressure measurement, rats were administered valproic acid in drinking water (0.71% wt/vol) or vehicle, with pressure measured weekly thereafter. Another set of rats were treated with hydralazine (25 mg/kg per day orally) to determine the pressure-independent effects of HDAC inhibition on hypertension. Following 20 weeks of treatment, heart function was measured using echocardiography, rats were euthanized, and heart tissue was collected for measurement of total reactive oxygen species, as well as proinflammatory cytokine, cardiac hypertrophic, and oxidative stress gene and protein expressions. Blood pressure, proinflammatory cytokines, hypertrophic markers, and reactive oxygen species were increased in SHR versus WKY rats. These changes were decreased in valproic acid-treated SHR rats, whereas hydralazine treatment only reduced blood pressure. These data indicate that long-term histone deacetylase inhibition, independent of the blood pressure response, reduces hypertrophic, proinflammatory, and hypertensive responses by decreasing reactive oxygen species and angiotensin II type1 receptor expression in the heart, demonstrating the importance of uncontrolled histone deacetylase activity in hypertension.