Insulin and the Brain: A Sweet Relationship With Intensive Care.

BACKGROUND: Insulin receptors (IRs) in the brain have unique molecular features and a characteristic pattern of distribution. Their possible functions extend beyond glucose utilization. In this systematic review, we explore the interactions between insulin and the brain and its implications for anesthesiologists, critical care physicians, and other medical disciplines. METHODS: A literature search of published preclinical and clinical studies between 1978 and 2014 was conducted, yielding 5996 articles. After applying inclusion and exclusion criteria, 92 studies were selected for this systematic review. RESULTS: The IRs have unique molecular features, pattern of distribution, and mechanism of action. It has effects on neuronal function, metabolism, and neurotransmission. The IRs are involved in neuronal apoptosis and neurodegenerative processes. CONCLUSION: In this systematic review, we present a close relationship between insulin and the brain, with discernible effects on memory, learning abilities, and motor functions. The potential therapeutic effects extend from acute brain insults such as traumatic brain injury, brain ischemia, and hemorrhage, to chronic neurodegenerative diseases such as Alzheimer and Parkinson disease. An understanding of the wider effects of insulin conveyed in this review will prompt anaesthesiologists and critical care physicians to consider its therapeutic potential and guide future studies.

Neurocritical care for intracranial haemorrhage: a systematic review of recent studies.

Intracerebral haemorrhage (ICH) is associated with significant early mortality (up to 50% at 30 days) and long-term morbidity (with permanent neurological deficits in 75-80% of patients) and represents a serious health issue worldwide. The past decade has seen a dramatic increase in clinical research on ICH diagnosis and treatment that has led to revision of the guidelines for the diagnosis and management of ICH from the American Heart Association and American Stroke Association in 2013. This systematic review reports recent clinical evidence (original studies published between September 2013 and July 2015) related to neurocritical care and intensive care unit management of patients with ICH. All but one publication included in this review report original studies related to managment of patients with intracerebral or subarachnoid haemorrhage. These include insights on risk stratification and neurocritical care or intensive care unit treatment, management of haemodynamic variables and mechanical ventilation (goal-directed fluid therapy, advanced haemodynamic monitoring, and avoidance of hyperoxia and hyperventilation), and pharmacological neuroprotection.

Pharmacological perioperative brain neuroprotection: a qualitative review of randomized clinical trials.

Perioperative cerebral damage may be associated with surgery and anaesthesia. Pharmacological perioperative neuroprotection is associated with conflicting results. In this qualitative review of randomized controlled clinical trials on perioperative pharmacological brain neuroprotection, we report the effects of tested therapies on new postoperative neurological deficit, postoperative cognitive decline (POCD), and mortality rate. Studies were identified from Cochrane Central Register and MEDLINE and by hand-searching. Of 5904 retrieved studies, 25 randomized trials met our inclusion criteria. Tested therapies were: lidocaine, thiopental, S(+)-ketamine, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate and xenon remacemide, atorvastatin, magnesium sulphate, erythropoietin, piracetam, rivastigmine, pegorgotein, and 17ß-estradiol. The use of atorvastatin and magnesium sulphate was associated with a lower incidence of new postoperative neurological deficit. The use of lidocaine, ketamine, and magnesium sulphate was associated with controversial results on POCD. The POCD did not differ between treated patients and control group for other tested drugs (thiopental, propofol, nimodipine, GM1 ganglioside, lexipafant, glutamate/aspartate, xenon, erythropoietin, remacemide, piracetam, rivastigmine, pegorgotein, and 17ß-estradiol). None of the tested drugs was associated with a reduction in mortality rate. Drugs with various mechanisms of action have been tested over time; current evidence suggests that pharmacological brain neuroprotection might reduce the incidence of new postoperative neurological deficits and POCD, while no benefits on perioperative mortality are described. Of importance from this review is the need for shared methodological approach when clinical studies on pharmacological neuroprotection are designed.

Anesthetic management of endovascular neurosurgical procedures in acute ischemic stroke patients: A systematic review of meta-analyses.

Restoration of cerebral circulation in the ischemic area is the most critical treatment task for reducing irreversible neuronal injury in ischemic stroke patients. The recanalización of appropriately selected patients became indispensable for improving clinical outcomes and resulted in the widespread revascularization techniques. There is no clear answer as to which anesthetic modality to use in ischemic stroke patients undergoing neuro-endovascular procedures. The purpose of this systematic review is to conduct a qualitative analysis of systematic reviews and meta-analyses (RSs & MAs) comparing general anesthesia and non-general anesthesia methods for cerebral endovascular interventions in acute ischemic stroke patients. We developed a protocol with the inclusion and exclusion criteria for matched publications and conducted a literature search in PubMed and Google Scholar. The literature search yielded 52 potential publications. Ten relevant RSs & MAs were included and analysed in this review. The decision about which anesthesia method to use for endovascular procedures in managing acute ischemic stroke patients should be made based on the patient's personal characteristics, pathophysiological phenotypes, clinical characteristics, and institutional experience.

Side effects of continuous intra-arterial infusion of nimodipine for management of resistant cerebral vasospasm in subarachnoid hemorrhage patients: A systematic review.

BACKGROUND: Cerebral vasospasm is a common complication of subarachnoid hemorrhage. Nimodipine is the most frequently used drug for cerebral vasospasm management and is the only approved medication that has been demonstrated to reduce ischemic complications, infarct size and improve neurological outcome after aneurismal subarachnoid hemorrhage. The main purpose of this systematic review was to conduct a comprehensive analysis of the main cerebral and extracerebral side effects of continuous intra-arterial infusion of nimodipine in management of delayed cerebral ischemia in subarachnoid hemorrhage patients. MATERIALS AND METHODS: A protocol with the inclusion and exclusion criteria for matched cases and the method of analysis were established and agreed by all authors. We defined the scope of this review to include articles (prospective and retrospective) reporting the side effects of continuous intra-arterial infusion of nimodipine in human subjects. PRISMA guidelines were used to conduct this systematic review. RESULTS: A total of 8 articles reporting 136 patients were included in the review and analyzed. The side effects associated with continuous intra-arterial infusion of nimodipine were arterial hypotention, heparin-induced thrombocytopenia, atrial fibrillation or flutter, infections, acute kidney injury, hepatic and gastro-intestinal side effects. CONCLUSION: The most frequent side effects reported in the articles included in this systematic review associated with the continuous intra-arterial infusion of nimodipine were arterial hypotension and heparin-induced thrombocytopenia. Intracerebral hemorrhage, the elevation of ICP, heart rhythm disorders, infectious complications, and thrombosis of the catheter might be also associated with CIAN. Future prospective studies are warranted to establish the risks and incidence of procedure-related side effects.

Systematic review of clinical evidence on postoperative delirium: literature search of original studies based on validated diagnostic scales.

BACKGROUND: Postoperative delirium is a serious complication that can occur within the 5th postoperative day. In 2017, the European Society of Anesthesiologists delivered dedicated guidelines that reported the need for routine monitoring using validated scales. OBJECTIVE: Aim of this systematic review is to identify clinical studies related to postoperative delirium that included postoperative monitoring with validated scales. DESIGN: Systematic review METHODS: Searched keywords included the following terms: postoperative, postsurgical, post anesthesia, anesthesia recovery, delirium, and confusion. Two researchers independently screened retrieved studies using a data extraction form. RESULTS: Literature search led to retrieve 6475 hits; of these, 260 studies (5.6% of the retrieved), published between 1987 and 2021, included in their methods a diagnostic workup with the use of a postoperative delirium validated scale and monitored patients for more than 24 h, therefore are qualified to be included in the present systematic review. CONCLUSION: In conclusion, available clinical literature on postoperative delirium relies on a limited number of studies, that included a validated diagnostic workup based on validated scales, extracted from a large series of studies that used inconsistent diagnostic criteria. In order to extract indications based on reliable evidence-based criteria, these are the studies that should be selectively considered. The analysis of these studies can also serve to design future projects and to test clinical hypothesis with a more standardized methodological approach.

Temperature management in acute brain injury: A systematic review of clinical evidence.

Temperature alterations in neurocritical care settings are common and have a striking effect on brain metabolism leading to or exacerbating neuronal injury. Hyperthermia worsens acute brain injury (ABI) patients outcome. However conclusive evidence linking control of temperature to improved outcome is still lacking. This review article report an update -results from clinical studies published between March 2006 and March 2020- on the relationship between hyperthermia or Target Temperature Management and functional outcome or mortality in ABI patients. MATERIALS AND METHODS: A systematic search of articles in PubMed and EMBASE database was accomplished. Only complete studies, published in English in peer-reviewed journals were included. RESULTS: A total of 63 articles into 5 subchapters are presented: acute ischemic stroke (17), subarachnoid hemorrhage (14), brain trauma (14), intracranial hemorrhage (8), and mixed acute brain injury (10). This evidence confirm and extend the negative impact of hyperthermia in ABI patients on worse functional outcome and higher mortality. In particular "early hyperthermia" in AIS patients seems to have a protective role have as promoting factor of clot lysis but no conclusive evidence is available. Normothermic TTM seems to have a positive effect on TBI patients in a reduced mortality rate compared to hypothermic TTM. CONCLUSIONS: Hyperthermia in ABI patients is associated with worse functional outcome and higher mortality. The use of normothermic TTM has an established indication only in TBI; further studies are needed to define the role and the indications of normothermic TTM in ABI patients.

Awake fiberoptic intubation in patients with stenosis of the upper airways: Utility of the laryngeal nerve block.

Awake fiberoptic intubation (AFOI) is mandatory to manage difficult airways. Superior laryngeal nerve block (SLNB) could reduce risks and improve patient comfort. The aim of this study is to assess the procedural comfort of SLNB during AFOI in a population of patients undergoing upper airway oncological surgery. Forty patients were randomized into two groups and were treated with continuous infusion of remifentanil, topic anesthesia and intercricoid block. In the study group (=20), SLNB was performed with lidocaine (L-SLNB); in the control group (n=20) SLNB was performed using saline (S-SLNB). AFOI was more comfortable in the L-SLNB group compared to S-SLNB patients [FOICS ≤ 1 in 18 patients (90%) L-SLNB; 2 (10%) S-SLNB (P <0.001)]. Intubation was faster in L-SLNB (47.45 ±15.38 sec) than S-SLNB (80.15 ±37.91 sec) (p <0.001). The SLNB procedure during AFOI is a safe and comfortable procedure in a population of patients undergoing upper airways surgery. Time to intubation was shorter in L-SLNB than in S-SLNB.

Short Report - Medical nutrition therapy for critically ill patients with COVID-19.

No Abstract Available.

Risk index for peri-operative atrial fibrillation in patients undergoing open intracranial neurosurgical procedures.

The aim of this prospective study was to determine the prevalence of pre-operative atrial fibrillation and the incidence of postoperative atrial fibrillation in patients undergoing elective or emergency intracranial neurosurgical procedures and the relation to survival and neurological outcome at 6-months follow-up compared to patients with sinus rhythm. A total of 2020 patients were enrolled; 1540 patients underwent elective procedures and 480 underwent emergency procedures. Prevalence of pre-operative atrial fibrillation was 3.7% in elective and 7.2% in emergency procedures (p = 0.0012). In patients undergoing elective cerebral procedures with pre-operative atrial fibrillation, compared to patients with sinus rhythm, 6-month neurological outcome and survival rate are similar. In patients undergoing emergency neurosurgical cerebral procedures, the presence of pre-operative atrial fibrillation is related to an increased risk of poor neurological outcome but with similar survival rate.

Influence of residual perfusion within the infarct zone on the natural history of left ventricular dysfunction after acute myocardial infarction: a myocardial contrast echocardiographic study.

OBJECTIVES: This study used myocardial contrast echocardiography to investigate the extent of residual perfusion within the infarct zone in a select group of patients with recently reperfused myocardial infarction and evaluated its influence on the ultimate infarct size. BACKGROUND: Limited information is available on the status of myocardial perfusion within postischemic dysfunctional segments at predischarge and on its influence on late regional and global functional recovery. METHODS: Twenty patients with acute myocardial infarction were selected for the study. Patients met the following inclusion criteria: 1) single-vessel coronary artery disease; 2) patency of infarct-related artery with persistent postischemic dysfunctional segments at predischarge; 3) stable clinical condition up to 6 months after hospital discharge. All selected patients underwent coronary angiography and myocardial contrast echocardiography before hospital discharge and repeated the echocardiographic examination 6 months later. Patients were grouped according to the pattern of contrast enhancement in predischarge dysfunctional segments. RESULTS: In nine patients (group I), the length of segments showing abnormal contraction coincided with that of the contrast defect segments. In the remaining 11 patients (group II), postischemic dysfunctional segments were partly or completely reperfused. There was no difference between the two groups in asynergic segment length at predischarge (7.3 +/- 2.5 vs. 7.2 +/- 4.3 cm, p = NS). At follow-up study, asynergic segment length was significantly reduced in group II patients, whereas no changes were observed in group I patients (from 7.2 +/- 4.3 to 4.7 +/- 3.7 cm, p < 0.005; and from 7.3 +/- 2.5 to 7.5 +/- 2.9 cm, p = NS, respectively). CONCLUSIONS: Among patients with a predischarge patent infarct-related artery, further improvement in regional and global function may be expected during follow-up when residual perfusion in the infarct zone is present.

Risk factors of incomplete distribution of cardioplegic solution during coronary artery grafting.

Myocardial distribution of cardioplegic solution infused by combined antegrade/retrograde routes was assessed with myocardial contrast echocardiography in 18 patients with chronic stable angina and three-vessel disease undergoing elective coronary artery bypass grafting. Overall myocardial opacification was significantly greater in retrograde than in antegrade cardioplegia (77.7% +/- 13.4% versus 59.1% +/- 15.7%; p = 0.0009). The difference was affected by collateral circulation, as pointed out by the significant interaction between coronary collateral circulation and percent of myocardial opacification after antegrade and retrograde cardioplegia (p = 0.002). When we performed multiple comparisons, in patients with good collaterals the opacification difference between antegrade and retrograde cardioplegia was not statistically significant (66.4% +/- 10.2% versus 76.0% +/- 15.2%; p = not significant), whereas in patients with poor collaterals myocardial opacification during retrograde cardioplegia was significantly greater (44.3% +/- 15.0% versus 81.2% +/- 9.0%; p < 0.02). During antegrade cardioplegia, patients with poor collaterals showed a lower degree of myocardial opacification than patients with good collaterals (44.3% +/- 15.0% versus 66.4% +/- 10.2%; p < 0.01). Our results show that retrograde cardioplegia in patients undergoing elective coronary artery bypass grafting offers no advantage over antegrade cardioplegia when collateral circulation is well developed. On the other hand, conventional aortic root infusion may not provide adequate myocardial protection in the subset of patients with significantly narrowed or occluded coronary arteries and poor collaterals.

Hyperinsulinemia and hypertension. Do intestinal hormones play a role?

Gastric inhibitory polypeptide (GIP) is one of the strongest insulinotropic gut factors. Its secretion is induced by oral (but not intravenous) glucose and it has been implicated in the pathogenesis of hyperinsulinemic states (NIDDM, obesity). To determine its relevance to hypertension, 54 subjects were studied: 26 normotensives (12 with and 14 without family history of essential hypertension), and 28 essential hypertensive subjects. Plasma glucose, serum insulin (IRI), and GIP were evaluated after a mixed meal containing a total of 82 g of carbohydrates, and 2 g sodium chloride. Venous blood was collected at baseline and every 15 min during a 3-h period. Baseline levels of glucose, IRI, and GIP were comparable in the three groups. At 30 min, however, IRI and GIP were higher in normotensives with a family history of hypertension and in established hypertensive versus control subjects. Both in normotensive and in hypertensive groups, glucose, IRI, and GIP responses to the meal were significantly correlated. Our data suggest the contribution of altered GIP secretion in the pathogenesis of hyperinsulinemia in essential hypertension.

Assessment of no-reflow phenomenon after acute myocardial infarction with harmonic angiography and intravenous pump infusion with Levovist: comparison with intracoronary contrast injection.

Myocardial contrast echocardiography (intracoronary application) has emerged as an accurate method to detect the "no-reflow phenomenon." To investigate the diagnostic value of harmonic angiography after intravenous infusion of Levovist in assessing "no-reflow," both intracoronary and intravenous contrast injections were performed in a group of patients with acute myocardial infarction. Seventeen consecutive patients with a successfully reperfused acute myocardial infarction within 6 hours of symptom onset were selected for this study. All patients underwent contrast echocardiography with harmonic angiography with Levovist (400 mg/mL, intravenous pump infusion, trigger intervals 1:4 to 1:8) and sonicated albumin (0.5 to 1 mL, intracoronary bolus) on day 1 after the achievement of a sustained coronary reflow. Myocardial perfusion was qualitatively assessed with a 12-segment model. The endocardial length of the residual contrast defect after reflow was also calculated. Forty-four of 204 segments were not analyzed after intravenous contrast echocardiography and 37 after intracoronary contrast echocardiography because of artifacts. Intracoronary and intravenous injections showed a perfusion defect in 31 (19%) segments, with a concordance of 89% (kappa coefficient, 0.72). Concordance in anteroseptal, anterolateral, and inferolateral segments was 95% (kappa = 0.92), 88% (kappa = 0.66), and 83% (kappa = 0.57), respectively. With intracoronary injection used as the reference method, intravenous injection had a sensitivity of 74% and a specificity of 93% for diagnosing contrast defects. The endocardial extent of no-reflow was 18 +/- 19 after intravenous and 21 +/- 17 after intracoronary contrast echocardiography (P = not significant). Intravenous contrast echocardiography with Levovist reliably identifies the no-reflow phenomenon after successful reperfusion, especially in acute anteroseptal myocardial infarction.

Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast echocardiography.

The case report subject is a patient with an old anteroseptal myocardial infarction and postinfarction angina who developed, over the years, a small left coronary-to-left ventricle fistula. The first coronary angiogram, performed 4 months after the infarction, was negative for coronary fistula. The diagnosis was made 3 years later, at repeat cardiac catheterization with myocardial contrast echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5% human albumin microbubbles generated a bright cloud of contrast entering the left ventricular cavity at the level of the distal third of the interventricular septum. Conversely, cineangiography failed to show on-line the fistulous communication that was evident only after careful cineangiographic reviewing. This case demonstrates the high efficacy of myocardial contrast echocardiography in identifying very small coronary fistulae.

Myocardial contrast enhancement after intravenous injection of sonicated albumin microbubbles: a transesophageal echocardiography dipyridamole study.

Myocardial opacification after intravenous injection of an echo-contrast agent is a major end point in contrast echocardiography, but it has not yet been obtained in human beings. We propose transesophageal contrast echocardiography as a clinical tool for the study of myocardial perfusion in human beings. Sonicated albumin microbubbles are bright ultrasound reflectors that cross the pulmonary vasculature after intravenous injection and show physiologic transit times through tissues. Transesophageal echocardiography uses ideal transducer frequency and acoustic window for in vivo detection of sonicated albumin microbubbles. We have studied 11 patients receiving peripheral vein bolus injection of sonicated albumin microbubbles during transesophageal echocardiography at baseline and during dipyridamole infusion. Images were recorded on videotape and digitized off-line. Quantitative measurements were made on 11 normally perfused myocardial segments by tracing a region of interest of greater than 100 pixels on frozen end-systolic frames, at baseline, and during dipyridamole infusion. Transpulmonary passage with full left ventricular cavity opacification was obtained in all injections. In 8 of 22 injections there was also transient left ventricular cavity attenuation. In all patients there was a marked opacification of the left ventricular outflow tract and aortic root. At baseline, mean signal intensity in the myocardium increased from 80 +/- 37 to 117 +/- 49 IU (p < 0.05) and during dipyridamole infusion increased from 84 +/- 28 to 146 +/- 36 IU (p < 0.001). The analysis of background-subtracted data showed that mean pixel intensity increased from baseline to dipyridamole contrast injection (from 37 +/- 15 to 62 +/- 19 IU; p < 0.01). The opacification of normally perfused left ventricular myocardium is feasible during transesophageal echocardiography because there is a significant increase in signal intensity versus background intensity. During dipyridamole infusion there is a further increase in signal intensity that probably reflects pharmacologically induced increase in myocardial blood flow.