Suitability of the forearm for non-invasive blood pressure measurement in children.

BACKGROUND: Measurement of forearm blood pressure (BP) in pediatric patients during general anesthesia is periodically employed despite a lack of evidence for this practice. Upper arm BP measurement may be impossible to perform for either patient or surgical reasons, and the forearm has theoretical benefits over the lower leg when an alternate site is required. We hypothesize that forearm BP measurement provides an accurate and reliable alternative to the upper arm. Published adult data do not support this hypothesis, and the little pediatric data published contain methodological shortcomings. METHODS: A dedicated, externally calibrated noninvasive oscillometer was used to compare BP measurements in the upper arm and ipsilateral forearm of pediatric patients undergoing general anesthesia prior to application of a surgical stimulus. Both upper arm BP and ipsilateral forearm BP were sequentially measured 20 seconds apart on 3 separate occasions with an appropriately sized cuff. The systolic, diastolic, and mean blood pressures were recorded under steady-state conditions. RESULTS: Thirty-five elective surgical patients aged 1 to 10 years were studied. The bias (±limits of agreement) for forearm minus upper arm blood pressures were as follows: mean BP -1.3 mm Hg (±7.2), diastolic BP -3.3 (±5.3), and systolic BP +3.2 mm Hg (±8.3). Differences greater than ±5 mm Hg occurred in 59% (systolic BP), 42% (diastolic BP), and 46% (mean BP) of all observations and greater than ±10 mm Hg in 17% (systolic BP), 8.6% (diastolic BP), and 15% (mean BP). CONCLUSION: The differences within mean ±1.96 standard deviations reside considerably outside the clinically accepted tolerance of ±5 mm Hg. Thus, the forearm may not be used interchangeably with upper limb BP readings in anesthetized healthy children. Future use of the forearm for BP measurement requires a validated anthropomorphically appropriate forearm cuff.

Ischemic stroke with extensive vasculopathy in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 is an autosomal dominant genetic disorder with multisystem manifestations including vascular abnormalities. The condition is also associated with an increased risk of both ischemic and hemorrhagic stroke. Here we report a case of a 60-year-old male with known neurofibromatosis who presented with right sided hemiparesis. Neuroimaging work-up revealed left internal carotid artery dissection and tandem occlusion of the left internal carotid artery and left middle cerebral artery. There was associated territorial ischemic infarction. The patient was found to have extensive intra and extra cranial vasculopathy including gross basilar dolichoectasia and a right-sided cervical internal carotid artery pseudoaneurysm. This case highlights the clinical significance of neurofibromatosis associated vasculopathy which can result in stroke.

Using Corneal Confocal Microscopy to Identify Therapeutic Agents for Diabetic Neuropathy.

Corneal confocal microscopy (CCM) is emerging as a tool for identifying small fiber neuropathy in both peripheral neuropathies and neurodegenerative disease of the central nervous system (CNS). The value of corneal nerves as biomarkers for efficacy of clinical interventions against small fiber neuropathy and neurodegenerative disease is less clear but may be supported by preclinical studies of investigational agents. We, therefore, used diverse investigational agents to assess concordance of efficacy against corneal nerve loss and peripheral neuropathy in a mouse model of diabetes. Ocular delivery of the peptides ciliary neurotrophic factor (CNTF) or the glucagon-like peptide (GLP) analog exendin-4, both of which prevent diabetic neuropathy when given systemically, restored corneal nerve density within 2 weeks. Similarly, ocular delivery of the muscarinic receptor antagonist cyclopentolate protected corneal nerve density while concurrently reversing indices of systemic peripheral neuropathy. Conversely, systemic delivery of the muscarinic antagonist glycopyrrolate, but not gallamine, prevented multiple indices of systemic peripheral neuropathy and concurrently protected against corneal nerve loss. These data highlight the potential for use of corneal nerve quantification by confocal microscopy as a bridging assay between in vitro and whole animal assays in drug development programs for neuroprotectants and support its use as a biomarker of efficacy against peripheral neuropathy.

The Impact of Intraoperative Donor Blood on Packed Red Blood Cell Transfusion During Deceased Donor Liver Transplantation: A Retrospective Cohort Study.

BACKGROUND: Blood from deceased organ donors, also known as donor blood (DB), has the potential to reduce the need for packed red blood cells (PRBCs) during liver transplantation (LT). We hypothesized that DB removed during organ procurement is a viable resource that could reduce the need for PRBCs during LT. METHODS: We retrospectively examined data on LT recipients aged over 18 y who underwent a deceased donor LT. The primary aim was to compare the incidence of PRBC transfusion in LT patients who received intraoperative DB (the DB group) to those who did not (the nondonor blood [NDB] group). RESULTS: After a propensity score matching process, 175 patients received DB and 175 did not. The median (first-third quartile) volume of DB transfused was 690.0 mL (500.0-900.0), equivalent to a median of 3.1 units (2.3-4.1). More patients in the NDB group received an intraoperative PRBC transfusion than in the DB group: 74.3% (95% confidence intervals, 67.8-80.8) compared with 60% (95% confidence intervals, 52.7-67.3); P = 0.004. The median number of PRBCs transfused intraoperatively was higher in the NDB group compared with the DB group: 3 units (0-6) compared with 2 units (0-4); P = 0.004. There were no significant differences observed in the secondary outcomes. CONCLUSIONS: Use of DB removed during organ procurement and reinfused to the recipient is a viable resource for reducing the requirements for PRBCs during LT. Use of DB minimizes the exposure of the recipient to multiple donor sources.

Insulin-like growth factor-1 activates AMPK to augment mitochondrial function and correct neuronal metabolism in sensory neurons in type 1 diabetes.

OBJECTIVE: Diabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes. We hypothesized that sub-optimal insulin-like growth factor 1 (IGF-1) signaling in diabetes drives loss of AMPK activity and mitochondrial function, both contributing to development of DSPN. METHODS: Age-matched control Sprague-Dawley rats and streptozotocin (STZ)-induced type 1 diabetic rats with/without IGF-1 therapy were used for in vivo studies. For in vitro studies, DRG neurons from control and STZ-diabetic rats were cultured and treated with/without IGF-1 in the presence or absence of inhibitors or siRNAs. RESULTS: Dysregulation of mRNAs for IGF-1, AMPKα2, ATP5a1 (subunit of ATPase), and PGC-1ß occurred in DRG of diabetic vs. control rats. IGF-1 up-regulated mRNA levels of these genes in cultured DRGs from control or diabetic rats. IGF-1 treatment of DRG cultures significantly (P < 0.05) increased phosphorylation of Akt, P70S6K, AMPK and acetyl-CoA carboxylase (ACC). Mitochondrial gene expression and oxygen consumption rate (spare respiratory capacity), ATP production, mtDNA/nDNA ratio and neurite outgrowth were augmented (P < 0.05). AMPK inhibitor, Compound C, or AMPKα1-specific siRNA suppressed IGF-1 elevation of mitochondrial function, mtDNA and neurite outgrowth. Diabetic rats treated with IGF-1 exhibited reversal of thermal hypoalgesia and, in a separate study, reversed the deficit in corneal nerve profiles. In diabetic rats, IGF-1 elevated the levels of AMPK and P70S6K phosphorylation, raised Complex IV-MTCO1 and Complex V-ATP5a protein expression, and restored the enzyme activities of Complex IV and I in the DRG. IGF-1 prevented TCA metabolite build-up in nerve. CONCLUSIONS: In DRG neuron cultures IGF-1 signals via AMPK to elevate mitochondrial function and drive axonal outgrowth. We propose that this signaling axis mediates IGF-1-dependent protection from distal dying-back of fibers in diabetic neuropathy.

Comparison of the WarmCloud and Bair Hugger Warming Devices for the Prevention of Intraoperative Hypothermia in Patients Undergoing Orthotopic Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND: The avoidance of hypothermia is vital during prolonged and open surgery to improve patient outcomes. Hypothermia is particularly common during orthotopic liver transplantation (OLT) and associated with undesirable physiological effects that can adversely impact on perioperative morbidity. The KanMed WarmCloud (Bromma, Sweden) is a revolutionary, closed-loop, warm-air heating mattress developed to maintain normothermia and prevent pressure sores during major surgery. The clinical effectiveness of the WarmCloud device during OLT is unknown. Therefore, we conducted a randomized controlled trial to determine whether the WarmCloud device reduces hypothermia and prevents pressure injuries compared with the Bair Hugger underbody warming device. METHODS: Patients were randomly allocated to receive either the WarmCloud or Bair Hugger warming device. Both groups also received other routine standardized multimodal thermoregulatory strategies. Temperatures were recorded by nasopharyngeal temperature probe at set time points during surgery. The primary endpoint was nasopharyngeal temperature recorded 5 minutes before reperfusion. Secondary endpoints included changes in temperature over the predefined intraoperative time points, number of patients whose nadir temperature was below 35.5°C and the development of pressure injuries during surgery. RESULTS: Twenty-six patients were recruited with 13 patients randomized to each group. One patient from the WarmCloud group was excluded because of a protocol violation. Baseline characteristics were similar. The mean (standard deviation) temperature before reperfusion was 36.0°C (0.7) in the WarmCloud group versus 36.3°C (0.6) in the Bairhugger group (P = 0.25). There were no statistical differences between the groups for any of the secondary endpoints. CONCLUSIONS: When combined with standardized multimodal thermoregulatory strategies, the WarmCloud device does not reduce hypothermia compared with the Bair Hugger device in patients undergoing OLT.

Effect of anaesthetic technique on immune cell infiltration in breast cancer: a follow-up pilot analysis of a prospective, randomised, investigator-masked study.

BACKGROUND: Live animal studies using an inoculation model of breast cancer indicate that anaesthetic drugs and techniques differentially affect cancer metastasis, inversely related to Natural Killer (NK) cell and T lymphocyte levels. Clinical histological studies demonstrate that the distribution of these immune cells and macrophages in intra-tumoral cancer tissue can predict prognosis and response to therapy. No study has evaluated whether the anaesthetic technique influences human breast cancer immune cell infiltration. MATERIALS AND METHODS: Excised breast cancer specimens from patients previously enrolled in an ongoing, prospective, randomised trial (NCT00418457) investigating the effect of anaesthetic technique on long-term breast cancer outcome were immunohistochemically stained to enable a colour deconvolution technique to summate marked immune cell infiltration: CD56 (NK cells), CD4 (T helper cells), CD8 (T suppressor cells) and CD68 (macrophages). Patients were randomised to receive either a propofol-paravertebral anaesthetic with continuing analgesia (PPA, n=12) or a balanced general anaesthesia with opioid analgesia (GA, n=16) for 24 h postoperatively. Investigators were masked to group allocation. RESULTS: Normalised positive intensity values, (median (interquartile range (IQR)), for CD56 were lower in GA121 (116-134) versus 136 (132-142), p=0.015. CD4 was also lower in GA10.9 (5.5-27.8) versus PPA 19.7 (14.4-83.5), p=0.03 but CD8 5.5 (4.0-9.75) versus 13.0 (5.0-14.5) respectively, p=0.24 and CD 68 infiltration 5.8 (3.25-8.75) versus 8.0 (3.0-8.75), p=0.74 were not significantly different. CONCLUSION: PPA induces increased levels of NK and T helper cell infiltration into breast cancer tissue compared with GA but not T suppressor cells or macro phages. This is consistent with the hypothesis that the anaesthetic technique may affect perioperative immune function conducive to resisting breast cancer recurrence and metastasis.