■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

Management of postoperative pain: A clinical practice guideline from the american pain society, the american society of regional anesthesia and pain medicine, and the american society of anesthesiologists' committee on regional anesthesia, executive committee, and administrative council.

tance, impaired drug clearance, and mild coagulopathy. Targeted interventions are required to effectively manage these side effects. Hypothermia does not decrease myocardial contractility or induce hypotension if hypovolemia is corrected, and preliminary evidence suggests that it can be safely used in patients with cardiac shock. Cardiac output will decrease due to hypothermiainduced bradycardia, but given that metabolic rate also decreases the balance between supply and demand, is usually maintained or improved. In contrast to deep hypothermia (<30°C), moderate hypothermia does not induce arrhythmias; indeed, the evidence suggests that arrhythmias can be prevented and/or more easily treated under hypothermic conditions. Conclusions: Therapeutic hypothermia is a highly promising treatment, but the potential side effects need to be properly managed particularly if prolonged treatment periods are required. Understanding the underlying mechanisms, awareness of physiological changes associated with cooling, and prevention of potential side effects are all key factors for its effective clinical usage. (Crit Care Med 2009; 37[Suppl.]:S186 –S202)

https://emcrit.org/wp-content/hypoarts/polderman%20mechs%20of%20hypothermia.pdf

Mechanisms of action, physiological effects, and complications of hypothermia.

Background and Purpose —The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (PETCO2) on MCA diameter and CFV.

Methods —Twelve subjects participated in a CO2 manipulation protocol and/or an LBNP protocol. In the CO2 manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO2 (hypercapnia), or they hyperventilated to ≈25 mm Hg PETCO2 (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of −20 and −40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols.

Results —Compared with normocapnia, hypercapnia produced increases in both PETCO2 (from 36±3 to 40±4 mm Hg, P <0.05) and CFV (from 63±4 to 80±6 cm/s, P <0.001) but did not change MCA diameters (from 2.9±0.3 to 2.8±0.3 mm). Hypocapnia produced decreases in both PETCO2 (24±2 mm Hg, P <0.005) and CFV (43±7 cm/s, P <0.001) compared with normocapnia, with no change in MCA diameters (from 2.9±0.3 to 2.9±0.4 mm). During −40 mm Hg LBNP, PETCO2 was not changed, but CFV (55±4 cm/s) was reduced from baseline (58±4 cm/s, P <0.05), with no change in MCA diameter.

Conclusions —Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in PETCO2.

https://ir.lib.uwo.ca/cgi/viewcontent.cgi?article=1028&context=kinpub

MRI Measures of Middle Cerebral Artery Diameter in Conscious Humans During Simulated Orthostasis

P RACTICE Advisories are systematically developed reports that are intended to assist decision-making in areas of patient care. Advisories provide a synthesis and analysis of expert opinion, clinical feasibility data, open forum commentary, and consensus surveys. Practice Advisories developed by the American Society of Anesthesiologists (ASA) are not intended as standards, guidelines, or absolute requirements, and their use cannot guarantee any specific outcome. They may be adopted, modified, or rejected according to clinical needs and constraints and are not intended to replace local institutional policies. Practice Advisories are not supported by scientific literature to the same degree as standards or guidelines because of the lack of sufficient numbers of adequately controlled studies. Practice Advisories are subject to periodic update or re-

/pdf/practice-advisory-for-preanesthesia-evaluation-an-updated-2r8cnap5be.pdf

Practice advisory for preanesthesia evaluation: an updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation.

Objectives: To determine the incidence and identify risk factors of critical incidents in an ICU. Design: Prospective observational study of consecutive patients admitted over 1 year to an ICU. Critical incidents were recorded using predefined criteria. Their causes and consequences were analysed. The causes were classified as technical failure, patient's underlying disease, or human errors (subclassified as planning, execution, or surveillance). The consequences were classified as lethal, leading to sequelae, prolonging the ICU stay, minor, or without consequences. The correlation between critical incidents and specific factors including patient's diagnosis and severity score, use of monitoring and therapeutic modalities was analysed by uni- and multivariate analysis. Setting: An 11-bed multidisciplinary ICU in a non-university teaching hospital. Patients: 1024 consecutive patients admitted to the ICU. Intervention: None. Measurementsandmainresults: The median length of ICU stay by the 1024 patients was 1.9 days. Of the 777 critical incidents reported 2% were due to technical failure and 67% to secondary to underlying disease. There were 241 human errors (31%) in 161 patients, evenly distributed among planning (n=75), execution (n=88), and surveillance (n=78). One error was lethal, two led to sequelae, 26% prolonged ICU stay, and 57% were minor and 16% without consequence. Errors with significant consequences were related mainly to planning. Human errors prolonged ICU stay by 425 patient-days, amounting to 15% of ICU time. Readmitted patients had more frequent and more severe critical incidents than primarily admitted patients. Conclusions: Critical incidents add morbidity, workload, and financial burden. A substantial proportion of them are related to human factors with dire consequences. Efforts must focus on timely, appropriate care to avoid planning and execution mishaps at the beginning of the ICU stay; surveillance intensity must be maintained, specially after the fourth day.

Human errors in a multidisciplinary intensive care unit: a 1-year prospective study

This study tested the hypotheses that 1) temperatures of "central" sites are similar in infants and children undergoing noncardiac surgery and 2) airway heating and humidification increases distal esophageal temperature. Twenty children were randomly assigned to receive 1) active airway humidification using an airway heater and humidifier set at 37 degrees C (N = 8), 2) passive airway humidification using a heat and moisture exchanger (N = 6), or 3) no airway humidification and/or heating (control, N = 6). There were no statistically significant differences between tympanic membrane, esophageal, rectal, and axillary temperatures. The temperatures of the peripheral skin surface (forearm and fingertip) were significantly lower than tympanic membrane temperature and significantly different from each other. Although esophageal and tympanic membrane temperatures in the entire group were similar, esophageal temperatures in patients receiving active and passive airway humidification were about 0.35 degrees C above tympanic temperatures after induction of anesthesia. In contrast, esophageal temperatures in patients without airway humidification were 0.25 degrees C below tympanic temperatures after induction of anesthesia. Esophageal-tympanic membrane temperature differences in the patients given active and passive humidification differed significantly from the corresponding sum in the control group at all times, but not from each other.

Intraoperative temperature monitoring sites in infants and children and the effect of inspired gas warming on esophageal temperature.

BACKGROUND:Pediatric tracheal intubation requires considerable expertise and can represent a challenge to many anesthesiologists. Confirmation of correct tracheal tube position relies on direct visualization or indirect measures, such as auscultation and capnography. These methods have varying sensi

Airway management in children: ultrasonography assessment of tracheal intubation in real time?

We tested the hypothesis that active and passive airway humidification minimize hypothermia in infants, but that maintaining normothermia does not decrease the duration of postoperative recovery. A circle system was used to ventilate the lungs of anesthetized, intubated infants who were randomly assigned to active airway humidification and warming with use of an MR450 Servo airway heater and humidifier set at 37 degrees C (n = 10), passive airway humidification with use of the Humid-Vent Mini heat and moisture exchanger placed between the Y-piece of the circle and the endotracheal tube (n = 10), or no airway humidification and heating (control, n = 10). Anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide in oxygen. The relative humidity of inspired respiratory gases was approximately 35% in the control group and approximately 90% in the group undergoing active airway humidification. Initial inspired humidity in the passive humidification group (45%) increased to approximately 80% after 1 h of anesthesia. Humidity differed significantly across groups at all times (P less than or equal to 0.05). Steady-state rectal temperatures (100-120 min after induction) were 36.2 +/- 0.7 degrees C in patients given active humidification and heating, 35.7 +/- 0.9 degrees C in the passively humidified group, and 35.2 +/- 0.4 degrees C in the control group (P less than or equal to 0.05 between each group). Recovery from general anesthesia was rapid in all patients and did not correlate with central temperature changes or type of humidification (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Passive or active inspired gas humidification increases thermal steady-state temperatures in anesthetized infants.

Tracheal intubation is frequently required in neonatal anaesthetic practice. Awake intubation is one method of securing the airway and in certain circumstances, for many anaesthetists, can be preferable to intubation following induction of anaesthesia. Previous studies have inferred that the elevation in anterior fontanelle pressure observed during tracheal intubation in neonates was caused by an increase in cerebral blood flow although it was never measured. In this study, direct methods were used to observe changes in the cerebral circulation. Thirteen neonates, ASA I to III (E), aged from 1 to 34 days of age were studied. Patients were randomized to receive either tracheal intubation awake or following induction of anaesthesia with thiopentone 5 mg.kg-1 and succinylcholine 2 mg.kg-1. Heart rate, systolic arterial blood pressure, anterior fontanelle pressure, cerebral blood flow velocity (using transcranial Doppler sonography) and oxygen saturation were recorded at the following intervals: baseline (not crying), after intravenous atropine 0.02 mg.kg-1, during laryngoscopy, immediately after insertion of the endotracheal tube, one and five minutes later. The use of atropine masked the cardiovascular responses to intubation. Whereas the change in anterior fontanelle pressure from baseline was different between the groups (P < 0.05), the cerebral blood flow velocity variables were not. The rise in anterior fontanelle pressure seen in the awake group may be attributed to a reduction of the venous outflow from the cranium thereby increasing cerebral blood volume and subsequently the intracranial pressure.

https://link.springer.com/content/pdf/10.1007/BF03009904.pdf

Bruno Bissonnette

Papers

Human errors in a multidisciplinary intensive care unit: a 1-year prospective study

Intraoperative temperature monitoring sites in infants and children and the effect of inspired gas warming on esophageal temperature.

Airway management in children: ultrasonography assessment of tracheal intubation in real time?

Passive or active inspired gas humidification increases thermal steady-state temperatures in anesthetized infants.

Awake intubation increases intracranial pressure without affecting cerebral blood flow velocity in infants