■ 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.

Chapter 5 – Thermoregulation: Physiology and Perioperative Disturbances

Purpose
To evaluate the tracheal intubating conditions when intubation time is determined by the onset time of the neuromuscular block either of the adductor pollicis (AP) or of the orbicularis oculi muscle (OO).

/pdf/evaluation-des-conditions-d-intubation-sous-rocuronium-16oh38k55f.pdf

Evaluation des conditions d’intubation sous rocuronium

Background To determine the effects of sevoflurane on cerebrovascular carbon dioxide reactivity (CCO2R), middle cerebral artery blood flow velocity (CBFV) was measured at different levels of P e ′CO2 by transcranial Doppler sonography in 16 ASA I or II children, aged 18 months to 7 yr undergoing elective urological surgery. Methods Anaesthesia comprised 1.0 MAC sevoflurane and air in 30% oxygen delivered through an Ayre's T piece by intermittent positive-pressure ventilation, and a caudal epidural block with 0.25% bupivacaine 1.0 ml kg−1 without epinephrine. P e ′CO2 was randomly adjusted to 25, 35, 45 and 55 mm Hg (3.3, 4.6, 5.9 and 7.2 kPa) with an exogenous source of CO2, while maintaining ventilation variables constant. Results CBFV increased as P e ′CO2 increased from 25 to 35, and to 45 mm Hg (P e ′CO2 from 45 to 55 mm Hg. Mean heart rate and arterial pressure remained constant. Conclusion CCO2R is preserved in healthy children anaesthetized with 1.0 MAC sevoflurane.

Cerebrovascular carbon dioxide reactivity in children anaesthetized with sevoflurane

Intraoperative hypothermia results largely from anesthetic-induced inhibition of tonic thermoregulatory vasoconstriction. Sufficient hypothermia, however, triggers peripheral vasoconstriction, which usually prevents further decrease in core temperature. The thermoregulatory effects of all volatile anesthetics have been tested in adults and/or children, but different anesthetics have not been directly compared. We therefore evaluated thermoregulatory responses during enflurane, isoflurane, and halothane administration. Anesthesia was maintained with 1 minimum alveolar anesthetic concentration (MAC) of halothane, isoflurane, or enflurane in 27 patients undergoing intraabdominal surgery. Patients were maintained normovolemic and normocapnic but were allowed to cool passively. A forearm minus fingertip, skin-temperature gradient of 4 degrees C identified significant vasoconstriction; the core temperature triggering vasoconstriction identified the threshold. Morphometric characteristics, initial core temperatures, ambient operating room temperatures, blood pressures, and anesthetic potencies were similar in each group. All eight patients given halothane vasoconstricted at a core temperature of 35.5 +/- 0.6 degrees C. Eight of the patients given isoflurane vasoconstricted at a core temperature of 35.2 +/- 0.5 degrees C. However, two others did not at minimum core temperatures of 34.0 and 33.8 degrees C. Only one patient given enflurane vasoconstricted at a core temperature of 34.6 degrees C. The other six patients never vasoconstricted, at minimum core temperatures of 33.6 +/- 0.4 degrees C. Our data indicate that enflurane profoundly inhibits thermoregulatory responses in children. The mechanism for this extraordinary inhibition remains unknown but does not result from any obvious anesthetic pharmacology or thermoregulatory physiology. We conclude that unwarmed pediatric patients will become colder when anesthetized with enflurane than with halothane or isoflurane.
(Anesth Analg 1996;83:595-9)

Bruno Bissonnette

Papers

Chapter 5 – Thermoregulation: Physiology and Perioperative Disturbances

Evaluation des conditions d’intubation sous rocuronium

Cerebrovascular carbon dioxide reactivity in children anaesthetized with sevoflurane

Enflurane decreases the threshold for vasoconstriction more than isoflurane or halothane

CHAPTER 6 – Thermoregulation: Physiology and Perioperative Disturbances