■ 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.

The pediatric airway: Historical concepts, new findings, and what matters

BACKGROUND Children may exhibit delayed emergence following maintenance of anesthesia with propofol or isoflurane. Desflurane is often used towards the end of procedures to facilitate emergence. This study evaluated the effect on middle cerebral artery blood flow velocity (Vmca) in anesthetized children when propofol or isoflurane was substituted with desflurane. METHODS Forty-two healthy children aged 1-6 years were enrolled. A standardized anesthetic induction was used. Anesthesia was maintained with remifentanil (0.5 microg.kg(-1) bolus followed by an infusion of 0.2 microg.kg(-1).min(-1)) and a randomly selected sequence of propofol/desflurane/propofol, desflurane/propofol/desflurane, isoflurane/desflurane/isoflurane or desflurane/isoflurane/desflurane. Propofol was administered to maintain a steady-state serum concentration of 3 microg.ml(-1). Desflurane and isoflurane were administered at age-corrected 1 MAC. Hemodynamic stability was maintained. Transcranial Doppler sonography was used to measure Vmca. Hemodynamic variables as well as Vmca were measured 30 min after skin incision and repeated 30 min after each change in anesthetic maintenance agent. RESULTS The mean age and weight was 2.3 +/- 1.3 years and 13.0 +/- 3.7 kg, respectively. The Vmca (mean) increased by 35% from 37.7 +/- 10.5 cm s(-1) to 57.8 +/- 14.6 cm s(-1) (P < 0.0001) when propofol was changed to desflurane but was unaffected when desflurane replaced isoflurane. CONCLUSION When propofol is changed to desflurane, cerebral blood flow velocity increases significantly in normal children. This cerebral vasodilatory effect may have important implications in the neurosurgical setting.

Cerebral blood flow velocity increases when propofol is changed to desflurane, but not when isoflurane is changed to desflurane in children.

Purpose: Laboratory experiments were performed to determine warming rates of albumin 5% at room temperature and human packed red blood cells (PRBCs) at 4~ in small volumes. Four methods used in clinical practice to warm volumes appropriate for neonates were studied. Methods: The fluids were warmed either by infusion through a fluid warmer with temperature-controlled coaxial tubing (Group I), immersion in a water bath at 37~ (Group II), placing pre-filled syringes (10 and 20 ml) between a circulating water mattress and a forced-air warming blanket (Group III), or placing the same syringes between the water mattress and cotton towels (Group IV). The temperature of each fluid was recorded for the next 60 sec after the bolus injection in group I and every five minutes for a total of 30 min for the other groups. The time constant of warming for each group was calculated. The time constant and the temperature reached after the warming period were compared among groups, Results: In group I 20 ml room temperature albumin 5% or 4~ blood reached temperatures of 36.9 _+ 1.5~ and 34.5 _ 2.3~ within 60 sec, respectively. This was faster than all other techniques used (P < 0.001). The time constants measured for the albumin and the PRBCs were 0.23 +- 0. I and 0.20 +_ 0.05 minutes respectively. After 15 min albumin and PRBCs in group II reached 35.5 +- 0.4~ and 33.4 _+ 0.3~ in group III reached 33.7 -+ 1.0C and 32.8 ~ 1.7C, and in group IV reached 29.5 _ 0. I~ and 23.3 -+ 0.8~ after 15 min respectively.

/pdf/laboratory-investigations-methods-for-warming-intravenous-3ddaibqd7w.pdf

Bruno Bissonnette

Papers

The pediatric airway: Historical concepts, new findings, and what matters

Cerebral blood flow velocity increases when propofol is changed to desflurane, but not when isoflurane is changed to desflurane in children.

Laboratory Investigations Methods for warming intravenous fluid in small volumes

No flow during low-flow cardiopulmonary bypass.

Room H, 10/17/2000 9: 00 AM - 11: 00 AM (PS) Effect of Nitrous Oxide on Cerebral Blood Flow Velocity in Children Anesthetised with Sevoflurane A-1285