|Shock - A reappraisal: The holistic approach.|
|Jump to Full Text|
|PMID: 22787348 Owner: NLM Status: In-Data-Review|
|Shock as reaction to life-threatening condition needs to be reclassified in a timely and more scientific synopsis. It is not possible or beneficial any longer to avoid a holistic approach in critical illness. Semantics of critical illness has often been unfriendly in the literature and a simplification with the elimination of conceptual pleonasms and misnomers under the exclusive light of physiology and physiopathology would be advantageous. Speaking one language to describe the same phenomenon worldwide is essential for understanding; moreover, it increases focus on characterization and significance of the phenomena.|
|Fabrizio Giuseppe Bonanno|
Related Documents :
|19857228 - Rhodopsin population genetics and local adaptation: variable dim-light vision in sand g...
15002778 - The effect of spatial heterogeneity and parasites on the evolution of host diversity.
25449338 - Spatial and temporal aspects of chromatic adaptation and their functional significance ...
7705628 - Genetic adaptation to captivity and inbreeding depression in small laboratory populatio...
24658388 - A fast, robust algorithm for power line interference cancellation in neural recording.
24149008 - Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.
|Type: Journal Article|
|Title: Journal of emergencies, trauma, and shock Volume: 5 ISSN: 0974-519X ISO Abbreviation: J Emerg Trauma Shock Publication Date: 2012 Apr|
|Created Date: 2012-07-12 Completed Date: - Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 101493921 Medline TA: J Emerg Trauma Shock Country: India|
|Languages: eng Pagination: 167-77 Citation Subset: -|
|Trauma Directorate, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.|
|APA/MLA Format Download EndNote Download BibTex|
Journal ID (nlm-ta): J Emerg Trauma Shock
Journal ID (iso-abbrev): J Emerg Trauma Shock
Journal ID (publisher-id): JETS
Publisher: Medknow Publications & Media Pvt Ltd, India
Copyright: © Journal of Emergencies, Trauma, and Shock
Received Day: 25 Month: 4 Year: 2011
Accepted Day: 12 Month: 6 Year: 2011
Print publication date: Season: Apr-Jun Year: 2012
Volume: 5 Issue: 2
First Page: 167 Last Page: 177
PubMed Id: 22787348
Publisher Id: JETS-5-167
|Shock - A reappraisal: The holistic approach|
|Fabrizio Giuseppe Bonannoaff1|
|Trauma Directorate, Chris Hani Baragwanath Hospital, Johannesburg, South Africa
|Correspondence: Address for correspondence: Dr. F G Bonanno, E-mail: firstname.lastname@example.org
The concept of critical illness comprises the definitions of shock/MODS/MOF, acute respiratory failure or cardiac/respiratory cardiac arrests, situations at imminent risk of death by generalized hypoxia or by circulatory arrest causing generalized hypoxia.
Critical illness pathways from physiology to exitus can be seen in a unifying concept and working frame, based on three considerations: biological phenomena and processes run simple routes under universal laws applicable to any branch of knowledge, aspect of life or nature, under the second principle of thermodynamics and the human body is subjected to the same laws – “as above as below as in as out”; nature has a metaphysical aim in everything that happens – “heaven is my thrown and earth is my footstool”; man's mind has obvious limits and restrictions in photographing a biological process, which run independently on our partial reading of nature, like trying to see a whole orange from a chunk of one of its segments not knowing what is above, below, behind, beyond, inside, outside, and on its sides – “You cannot see the forest from a tree but can see a tree from the forest.”
Shock is an acute or hyperacute physiological derangement, a systemic syndrome characterized by signs and symptoms that are the response of different organs to a situation of hypoperfusion for their cells basic metabolic needs. Perfusion means oxygen and nutrients delivery via blood flow.
Each organ controls locally the blood supply according to its needs by modulating a stable influx of blood with oxygen and nutrients in the microcirculation within an ample pressure range by local flow regulation mechanisms (metabolic and/or myogenic theories). In normal conditions low oxygen or PH, and high CO2, osmolality, K+, lactate or temperature, vasodilate microcirculation; the opposite trends vasoconstrict it. In trauma and sepsis, other factors affect microcirculation baseline status. Nitric oxide is secreted in many types of cells to vasodilate microcirculation in normal and pathological circumstances acting on guanylyl cyclase to produce cyclic guanosine monophosphate, which causes vascular smooth muscle relaxation.
Systemic vascular reflexes, age, and vessel-integrity dependent, are also triggered. These reflexes cause vasoconstriction of arterioles that raises blood pressure in conjunction with fluids’ administration (compensated shock) up to a certain point beyond which if the causa prima and/or primum movens persist, a decompensation occurs (decompensated shock), as signaled by fluid-resistant hypotension from loss of arteriolar tone.
The innate localized inflammatory response (LIR) is an ontogenetic and phylogenetic response to external or internal insult such as an injury or bacterial infection, which may spread systemically (SIR) when not controlled in situ or at its origin. SIR cannot occur in hemorrhage because its actors get lost in the extravascular spaces; in hemorrhage scenario it has a role, though, in a second hit from ischemia of the gut from which SIR and/or ischemia-reperfusion (I-R) phenomenon spring.
Hormonal and cellular factors are also invariably released locally and systemically in any shock or situation of trauma, infection, systemic inflammation, and hypoperfusion, and represent a generalized body response to a scenario of danger or stress.
Organs are affected by hypoxia following hypoperfusion in hemorrhagic shock (HS) and cardiogenic shock (CS) or by the direct toxic effect and higher oxygen demand of the inflammatory shock (IS).
Whether it is pump failure, hemorrhage or inflammation/infection, the end result of those mechanisms, when not corrected, reversed or arrested, is the same: at the end all shocks kill with different aetiologies and at different speeds as effect and result of generalized hypoxia.
A synopsis of the different speeds of the different etiologies and mechanisms leading to exitus is given in [Figure 1].
Whatever the etiology the determinant biological function, the funnel to exitus, is and remains the loss of the capacity to produce energy.
The body firstly compensates with natural mechanisms at to a certain point beyond which shock becomes compensated and full-blown. If tissue perfusion is persistently impaired and not corrected, the cellular dysfunction and organ failure becomes irreversible. No or inadequate intervention during the stage of decompensation leads to the so-called no-return point (NRP), where all shocks enter a predeath agonic stage and exhibit universal hypodynamic features of unresponsiveness to catecholamines, reduced metabolism, hypothermia, and reduced oxygen consumption with increased systemic venous oxygen saturation (SvO2) independently on shock etiology. Irreversible shocks in the end will enter a predeath agonic stage and exhibit universal hypodynamic features of unresponsiveness to catecholamines, reduced metabolism, hypothermia, and reduced oxygen consumption independently on shock etiology.[1, 2] Coagulopathy as DIC kills by occluding the microcirculation (arterioles, capillaries, venulae) and causing generalized hypoxia; hypothermia and acidosis kill by freezing and impairing life-indispensable enzymatic processes and by dampening life-saving responses. Terminal primary hypothermia cannot be reversed, is accompanied by terminal coagulopathy and indicates energy-production failure; terminal coagulopathy manifests with bleeding distant to any possible injury or tissue damage site, for example, mouth gush; and irreversible acidosis impairs endogenous and exogenous catecholamines response.
The passage from reversible to irreversible shock occurs at two no-return points: arteriole and mitochondria [Figure 2]. By NRP it is meant the point beyond which the arterioles–capillaries system or/and the cellular mitochondria cease functioning as result of an acute or persistent hypoxia. The first system cannot respond anymore to the oxygen/pressures/electric signals variations-stagnant hypoxia with no capillary blanching and reflow to digital pressure in superficial body areas displaying peripheral mottled cyanosis is a known sign of irreversibility and imminent death –and the second one cannot produce energy.
Theorized mechanisms of vasomotor paralysis partly involve ATP depletion or reactive oxygen species (ROS) inhibiting nitric oxide (NO) or NO dysfunction from other causes.
At cellular mitochondrial level NRP is reached at the disruption of any of the four main enzymatic pathways: inhibition of the formation of acetyl-coenzyme A, essential for the passage from the Krebs cycle to the phosphorylative oxidation mechanism of ATP formation; inhibition of cytochrome oxidase by an excess of NO in completion with O2, essential for oxidation and electrons transfer on the inner mitochondrial membrane; electron-transfer enzymes inhibition in the internal mitochondrial membrane by the interaction of NO with ROS formed in condition of inflammation, sepsis and I-R; reduction of the content of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide oxidized (NAD/NAD+), essential reducing (electrons donors) agents in the redox reaction ending with ATP formation by oxidative phosphorylation and formation of CO2 and H+, due to their exhaustion in partnering with Poly ADP-ribose polymerase (PARP-1) in trying to repair the damage to DNA done by ROS, end-product of the inflammatory response.
Adrenal insufficiency has also been associated with vasomotor paralysis and may represent a contributing factor probably linked to the cortisone role in maintaining cells membranes stabilization.
NRP is independent and not correlated to macrocirculation. This is why macrocirculation known variables cannot be relied upon for monitoring and prevention purposes. This is why patients suddenly die, as soon NRP is reached, despite seemingly normal or normalizing macrocirculation.
Because of the impossibility of manipulating the energy factory at this stage, the integrity of the microcirculation has a vital role in the prevention and management of critical illness.
The microcirculation-ecosystem failure is the conditio sine qua non for irreversibility in all shocks. While macrocirculation is merely a tank supplying microcirculation, microcirculation is the sancta sanctorum of life; it is the where and why we live, die and get sick; it is “will of life and its mystery” [Figure 3].
Ultimate shock, multiple organs dysfunction (MOD) and multiple organs failure (MOF) are in fact synonymous. All above terms simply describe a situation of progressive multiorgan deterioration pari passu with the worsening of the cellular hypoxia as response to a situation of inadequate perfusion to maintain their basic metabolic/energetic needs, and according to a well-defined strategy of the body to divert blood toward nobler organs. Semiological difference is in the presence (in shock) or absence (in MOD/MOF) of clinical hypotension. Semantically, the word “shock” emphasizes the hemodynamic moment and MOD/MOF emphasizes the progressive degrees of the cellular effects of shock.
The definition of shock as discrepancy, imbalance between oxygen delivery and consumption is another truthful, accurate, and comprehensive definition, stressing the core-problem at cellular level instead of the body response to a scenario of hypoxemia that may become hypoxia. It has nevertheless two weaknesses as it does not highlight the basic fact that hypoxemia is due to circulatory failure and includes the definition of respiratory failure by lung dysfunction or failure as cause of hypoxemia [Table 1].
Shock classification has been revised and reelaborated based on semantics, etiology, pathophysiology, and mechanism of cellular hypoxia [Figure 4] following i) the understanding of the role of the systemic inflammatory response to any uncontrolled local insult, ii) the relevance of the IR phenomenon in many pathological processes in critical illness, and iii) the focus that microcirculation is having as crucial site for perfusion and scavenging.
There are only three types of shock or generalized low/inadequate perfusion states: the CS, HS, and IS. HS and CS are caused by scarce perfusion/low offer and IS by inadequate perfusion/high demand as for maldistribution. IS is the optimal umbrella term that should be used for describing shock features as result of persistent, accentuated, acute or acute-on-chronic SIR, or of systemic I-R injury, caused by a LIR to sepsis or local I-R phenomenon that have not been controlled locally. The three main shocks differ in the primum movens, ie, the initial circulation variable that becomes deranged: HS is a failure of the peripheral circulation that has its initial deranged variables in the blood volume and venous return, and to follow, cardiac output/mean arterial pressure; in CS is the pump that fails and has its initial deranged variables in cardiac output/mean arterial pressure; in IS the microcirculation is affected while the initial deranged macrocirculation variable is the total peripheral resistance hit by SIR or by I-R phenomenon.
CS is a central shock sharing all macro and micro-hemodynamic and metabolic features of HS by which it differs only in the primary deranged macro-circulatory variable (pump/cardiac output vs venous return). Whereas the heart in the other two shocks behaves as a compensatory organ to the situation created by the initially deranged hemodynamic variable with an augmentation of frequency in HS and frequency/stroke volume in IS, in CS it is the pump failure itself the primum movens and causa prima of the derangement in the same time.
Of the two peripheral shocks, while HS is a blood-tank disorder affecting mainly and initially the macrocirculation, IS is specifically a microcirculation derangement. Microcirculation in HS is not affected until the terminal stages when the vasomotor response of arterioles is impaired from hypoxia of the endothelium, indicating irreversibility; in IS microcirculation is instead the primary target of SIR by bacterial endotoxin/lipopolysaccharide (LPS), or of I-R in not bacterial toxins (burns, pancreatitis, persistent, or complicated intestinal obstruction (IO), ischemic necrosis-gangrene, crush injury/I-R phenomenon). IS is an optimal umbrella term for describing shock features caused by sepsis or tissue damage, as result of persistent, accentuated, acute or acute-on-chronic SIR or I-R phenomenon. In 1971, Weil and Shubin had already envisaged and suggested the right classification identifying the term of distributive shock (DS) to indicate the maldistribution of perfusion at the microcirculation level. DS or IS shock causes ineffective perfusion because of: (1) a maldistribution of blood flow (despite a normal or elevated cardiac output) whose complex end-result is “dysoxic hypoxia” of the affected “life-unit”[8–11] and/or (2) impaired use of substrate due to defects in cellular oxygen utilization.
Continuous change in terminology to describe essentially the same phenomena has not helped understanding the core of inflammatory phenomena of critical illness. The random-cumulative character of the disorder sepsis/systemic inflammation,[13–15] the fact that hypoxemia installs early long before not-fluid respondent hypotension,[16–19] which defines septic shock,[20, 21] and the fact that the hemodynamic and organ derangement in the microcirculation, ie, oxygen maldistribution and disoxyc hypoxia, are independent and unaffected by the compensatory hyperdynamic circulation maintaining normal levels of blood pressure,[22–25] make the actual consensus-terminology rather feeble and arguable. The distinction between sepsis (infection + SIR), severe sepsis (sepsis + MOD), and septic shock (sepsis or severe sepsis + hypotension and hypoperfusion)[26–29] is as a matter of fact of scarce practical utility: those terms describe clinically elicitable manifestations of the progressing disorder at the macroscopic level only. Emphasis instead should be on the actually occurring microcirculatory changes, de facto dictating the orchestra of the disorder. The distinction between “severe sepsis” and “septic shock” is academic and not practical, due to the fact that by the time hypotension installs at full blown septic shock, the hemodynamic and organ derangement in the microcirculation, ie, oxygen maldistribution and disoxyc hypoxia are already in act despite the compensatory hyperdynamic circulation maintains normal levels of blood pressure. It does not help management either: due to the nature of the disorder, it is intuitive that not as much the early, but actually the earliest intervention possibly at the “sepsis” phase, would yield an even further decrease of mortality at the minimum possible terms than an early intervention within six hours from “severe sepsis/septic shock” insurgence. Moreover, what is the difference between “sepsis” and the old concept described as “septicemia”? Due to the continuous bit-by-bit ingress in the circulation of LPS, endotoxins, toxins, and inflammatory and cellular mediators and factors from a primary source of inflammation and the modulating actions of the natural counteracting mechanisms present in the blood, IS ensues as a progressive cumulative random derangement of ‘life-units’ within an organ and in multiple organs, independent on their priority in the economy and organization of the human body like instead it occurs in HS. More life-units are hit (arteriole-capillaries network tissues), the faster dysfunction and then failure occur. At some stage, the MOF becomes irreversible.
HS and CS are instead totalitarian organ-derangements from start, against which the body answers first by trying to safeguard and direct blood toward nobler organs from less noble ones in an inverse priority pattern within the context of body economy and functions. HS is therefore a quantitative problem of perfusion, IS a distributive one, ie, there is enough oxygen and substrates (perfusion) but it is mal-distributed in the microcirculation with some capillary beds receiving more oxygen than needed and others no or inadequate oxygen.
All shocks in full blown out phase are effectively vasoconstrictors, including the IS. What makes septic shock (SS) different from the other variants of IS is the initial hyperdynamic response of SS, LPS and other bacterial toxins mediated, that is responsible of the hyperdynamic, physiologically compensatory, and vasodilatatory phase.
By the hyperdynamic phase of SS, it is defined that clinic-metabolic-haemodynamic scenario characterized by increased temperature, elevated cardiac output, increased oxygen delivery (DO2), decreased systemic vascular resistance [with or without decreases in mean arterial blood pressure (MAP)], and increased tissue oxygen consumption (VO2), in response to a need for increased oxygen delivery before pathological supply dependence reaches the critical extraction rate point.[31–36] The hyperdynamic phase is not elicitable in IS states that are not septic shock. Only one explanation can account for this exception: the influence that LPS and some inflammatory mediators triggered by LPS have directly on the hypothalamus and the temperature controlling mechanisms nonetheless the more intense structural damage to microcirculation eliciting a more marked compensatory response. The increased temperature increases vasodilation, decreases TPR, increases oxygen consumption, and decreases blood pressure; by increasing oxygen consumption, it also calls for further vasodilatation and decrease of pressure. Pyrexia in the other inflammatory states is mild and the result of toxins-mediated metabolic raise of temperature rather than direct strong effect on the temperature regulating centers like the one that occurs in presence of interleukin-8 (IL-8) induced by LPS. The hyperdynamic phase of SS/IS must therefore be seen as similar to the flow-catabolic phase from the metabolic aspect, as systemic hyperbolic extension of the nutrients/lack of oxygen theory of local blood-flow control with increased metabolism and temperature, and increased oxygen consumption; it is also similar from the hemodynamic aspect to the systemic posttraumatic inflammatory response of blunt trauma without hemorrhage. The hyperdynamic response distinguishes and specifies SS from all other IS as for the specific effects of bacteria on temperature control mechanisms on hypothalamus and the structural damage that the Gram-negative bacteria induce in the endothelium. As a form of compensated shock, it differs from the compensated HS on the hemodynamic type of compensation, vasodilatative one, vasoconstricting the other. BP can be normal or low in hyperdynamic SS. The fact that Hyperdynamic SS responds to fluid makes it a compensated partial incomplete shock. Recent consensus on the definition of SS as a matter of fact stresses hypotension not responding to fluid challenge as a defining aspect of septic/IS[20, 21] whereas the hyperdynamic phase is instead by definition fluid-respondent.
Terms like toxic shock (TS), given away for unknown reasons to gynaecologists to describe a variant of a Gram-positive exotoxin septic shock, should be reabsorbed in the terminology of critical illness to describe a more comprehensive derangement characterized by tissue damage occurring in burns,[38, 39] acute necrotizing pancreatitis (ANP),[40–45] necrosis/gangrene, persistent or close-loop IO, which should also be included in the inflammatory category on the basis that mortality is usually mainly related to primary or secondary hit MOD/MOF driven by SIR/IR rather than to hypovolemia from fluids losses and sequestration. Acute necrotizing pancreatitis is characterized by a local (pancreatic and peripancreatic) release of proteolytic enzymes and inflammatory mediators, eventually spreading systemically. Lungs are regularly affected in ANP and kidney dysfunction is a frequent problem. The incriminated enzymes and mediators responsible of SIR and MOD in ANP are proteolytic enzymes from lysosomes (trypsinogen/trypsin, amylase, lipase, phospholipase, elastase, activating enzymes) and inflammatory cytokins (interleukins, tumor necrosis factor, bradykinin, platelet activating factor). Toxemia from burns is none other than I/R and/or a SIR caused by the burn injury. The same mediators (histamine, complement, prostaglandins, leukotrienes, kinins et al.) are released from the injured site and act systemically by increasing capillary permeability and edema. In severe burns thermal injury also causes direct cellular damage with decrease of the transmembrane potential resulting in increased intracellular sodium and depletion of extracellular one. Shock is therefore cause of mortality in burns and is directly correlated to the extent of injury from the toxic effect more than hypovolemia. Crush syndrome[47–49] is form of IR phenomenon[50–54] caused by damage to tissues from pressure resulting in ischemia as causa prima, with subsequent relief of the causative agents causing reversal of inflammatory/toxic mediators and factors in the systemic circulation.
The classical I-R phenomenon is seen in limbs or gut after reperfusion, or after failed or delayed treatment of ischemia. Semeiologically, all localized I-R phenomena such as any posttraumatic or burn necrosis, ischemic necrosis, especially if gangrenous, tissue infection with gangrene or pancreatic autolysis, trigger in variable ways the same events. The co-presence of vasoconstriction and increase of vascular permeability recalls closely the effects of I-R phenomenon elicited in laboratory.[51, 54] Generalized or systemic I-R phenomenon from not septic etiology and SIR can be seen as similar clinical entities but with different etiology [Figure 4]. Difference can be sought in a primary inflammatory and/or infective etiology of SIR and ischemic etiology of I-R phenomenon, but clinically both of them cause clinical hypotension and distant organs ischemia, and characterize the second-hit of physiological deterioration.
Likewise, traumatic shock, term now in disuse from critical care terminology, should also be reinstated to describe a form of shock occurring in severe blunt multiple organs trauma that if severe leads to immediate or rapid death following massive intravascular fluid loss into traumatized tissues extravascular spaces due to overwhelming SIR before concomitant hemorrhages have progressed to irreversible HS.[55–57] It can be considered the systemic equivalent of a crush injury, a generalized hyperacute I-R phenomenon that is inflammatory and not hemorrhagic in nature. SIR-hyperacute hypotension in these cases overwhelms in speed, action, and severity the body counteracting defensive-modulating mechanisms. Even the vasoconstrictive effect of I-R on microcirculation is overwhelmed by the rapidity of the massive severe SIR; it can in fact have time to occur only if the patient survives the impact. If the patient survives the impact phase of massive SIR, the I-R effect on microcirculation determines prognosis on survivors. Post-traumatic inflammatory response (PTIR) is a more suitable definition for this post-traumatic overwhelming SIR, which is so fast and massive to override body counteracting modulating mechanisms before concomitant hemorrhage/s and/or I-R phenomenon have progressed to a situation of irreversible shock.[5, 58–60] PTIR can also be caused by severe massive burns and other massive severe chemical or physical burns, before the toxic effects become main pathological driver. A mild form and incomplete shock occurs during any surgery as for the tissue necrosis and injury caused by the surgical procedures.
The contribution of the spinal cord acute derangement to PTIR following blunt trauma is still unexplored. Besides the well known role in hemodynamic control the autonomic nervous system may well be involved in our immune/inflammatory response.
A mix pattern hemorrhagic/inflammatory cannot occur synchronously as the inflammatory lava is lost with the blood loss and hemorrhage remains the primary or preponderant derangement. It can however manifest in a blunt trauma not immediately fatal with significant or multiple parenchymal hematoma or, to make a specific example, a liver or retroperitoneal hematoma, where hemorrhage occurs later and was missed because slow (secondary hemorrhage), in a background of unresolved inflammatory response to toxins from the hematoma or contused necrotic tissues first , and from infected bile or urine extravasation afterwards. In such scenarios, the hemorrhage at some point will characterize the picture and complicate physiology, causing an early MOF/MOF on the background of an already predisposed microcirculation/cellular microcosm affected by flow maldistribution and high oxygen demand. In such mixed pictures, whether started by hemorrhage or by sepsis/inflammation, the patho-physiological mechanisms potentiate and overlap each other often speeding up exitus.
All above terms, toxic shock and traumatic shock, likewise post-traumatic inflammatory response, should be reintroduced in medical terminology and retrieve their original meaning in the description of such specific categories of shock.
Some conditions, namely postspinal or posttraumatic neurogenic hypotension (NH), severe dehydration (SD), acute adrenal insufficiency (AAI), cannot be considered as shocks as the microcirculation and the cellular ecosystem with the core equations DO2/VO2 and O2ER are never affected and their manifestations are confined mainly to a decrease blood pressure only. Acute adrenal insufficiency (AAI) is often complication of SS rather than a primary adrenal disorder, an epiphenomenon secondary to the hypothalamic-pituitary-adrenal axis exhaustion in producing adrenocorticotropic hormone (ACTH) and cortisone following protracted stress response. Likewise ARDS and DIC,[62–64] AAI is a secondary manifestation, an epiphenomenon and side-effect of the systemic coagulopathy/inflammation phenomena accompanying shock. It should not be included among shock states. Acute anaphylactic reaction (AAR) is characterized by rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability as result mainly of the release of histamine by mast cells and basophiles triggered by IgE-specific antigens interaction. The DO2/VO2 ratio is not affected by the vasodilatation and bronchoconstriction. AAR in fact kills by acute CS/cardiac arrest or acute respiratory failure by bronchospasm.[65, 66] They are rather pseudo-shocks [Table 2].
Some other conditions, namely cardio-pulmonary by-pass (CPBP) and extracoroporeal membrane oxygenation (ECMO) syndromes, acute haemolytic anaemia, and severe malaria, as highlighted by Elbers and Ince, and the intraoperative insult per se with all the tissues disruption and iatrogenic damage, and at some extent the hyperdynamic phase of the SS, can all be regarded as shocks despite not exhibiting the classical full blown clinical picture and each actually representing specific accentuated single aspects of the whole spectrum of DS/IS. They should be seen as partial or incomplete shocks as they occur only during and alongside the causa prima or primum movens and cease on the ceasing of it, contrarily to standard inflammatory and HS by definition continuing with effects on the DO2/VO2 equation even long after the insult has been dealt with or has stopped [Table 2]. The CPBP circuit activates SIR;[68, 69] in acute hemolytic anemia or malaria, red-blood cells are deformed and occlude capillaries. In CPBP and ECMO circuits hyperoxia causes reflex arteriolar vasoconstriction and reduction in functional capillary density and distributive microcirculatory alterations, and hemodilution causes a decrease in blood viscosity, altered red-blood cell rigidity and functional shunting of the microcirculation. As for the Poiseuille and Bernoulli laws, reduced blood viscosity results in a reduction in longitudinal capillary pressure gradient, following reduced resistance, and a fall of capillary flow. In severe malaria and sickle cells acute crisis, capillaries are occluded by rigidity and aggregation of white and red blood cells.
The nonsubstitutable function of RBCs integrity in regulating microcirculation has been confirmed experimentally and clinically.[73–76] RBC deformability after trauma and HS leads to the microcirculatory dysfunction and clinical manifestations of organ failure. An amelioration of microcirculation after discontinuation of the intra-aortic balloon-pump in CS has also been noted. This can be due to several factors such as endothelin release from the thoracic aorta pressure by the balloon during diastole phase with distal microcirculation vasoconstriction, red-blood cells being mechanically damaged and losing their NO-production capacity, reflex electrical signals from proximal to distal circulation due to the stretch of the wall during the diastole phase, RBC structural proteins alteration.
Any insult to normal physiology triggers a hemodynamic response, a cellular-inflammatory-coagulatory response and a humoral-metabolic response by the sympathico-adrenal and the hypothalamic-pituitary-adrenal axis. The latter is a generic alarm system called into action by afferent stimulation such as pain, pressure, hypovolaemia, hypothermia, hyperthermia, hypoxia, necrosis, infection, wound, and PH unbalance. Hence, in any shock or condition potentially leading or accompanying shock, such a response manifests. The result of this reaction is the discharge in the systemic circulation of adreno-cortico-tropic hormone (ACTH-corticotrophin), corticosteroids, vasopressin-anti-diuretic hormone (ADH), aldosterone/renin-angiotensin system (A/RAS), catecholamines, insulin, and glucagon in a speed and manner directly relative to the quantity, quality, and duration of the stimuli.
To this standard biological response is to be added the release, locally and systemically from and around the site of “impact,” of inflammatory mediators, humoral and cellular factors, composing the basic immunitary response. This innate response is effectuated in infection and blunt trauma, where is early and preponderant in not hemorrhagic trauma and late in blunt hemorrhagic trauma.
The cellular-metabolic-hormonal response is also parallel and synchronous with the hemodynamic and respiratory reflex-responses and has been known for years.
At the moment of the impact with the causative mechanical factor in the immediate – Ebb phase – there is a black-out situation with peak reduction of metabolism, reduced oxygen consumption, reduced temperature, reduced insulin discharge, and increased fatty acids and lactic acid; catecholamines release is also increased causing a decrease of cardiac output and an increase of heart rate. This can be considered as a hyperacute stress-alarm reaction very similar to the stress-alarm reaction following a psychological or environmental stress. Clinically this reaction results in vasoconstriction, hypertension, tachycardia, and temporary control of the ventilation. This phase is triggered mainly by nociceptive stimuli. Teleologically, this “impact” phase is meant to limit the amount and duration of the injury.
It soon follows a – flow phase – characterized by an early catabolic-hypermetabolic period with: increased proteins breakdown quantitatively superior to increased synthesis (negative nitrogen balance), which differentiates flow-phase from starvation where both synthesis and degradation are reduced; weight loss; liver catecholamine-mediated glycogenolysis for a day or so, followed by gluconeogenesis; cortisol and ACTH increase; increase, but with resistance to, by tissues, of autogenous insulin; normalization of lipolysis; increase of temperature and oxygen consumption; initial increase of sodium, chloride and water retention in the circulation that is ADH and A/RAS mediated but later normalizes; intracellular sodium, water and chloride retention and potassium extracellular extrusion following cellular membrane potentials disruption; fluid extravasation through endothelium following increase of permeability and of hydrostatic pressure; growth hormone and prolactin increase; glucagon and thyroxin increase; catecholamine-mediated lactic acid and glucose level increases; increase of oxygen consumption, cardiac output, temperature and resting energy expenditure. The hepatic synthesis of acute phase proteins acting as markers of catabolism/hypermetabolism such as fibrinogen, C-reactive protein, haptoglobulins, complement system proteins, cytokines and interleukins, is increased. The metaphysical aim of this phase is to increase cardiovascular function, preserve fluids, and increase the supply of substrates following an increase of demand. Resuscitation buffers, contains, the catabolic phase but cannot abolish it. These alterations remain until the catabolic period stops, or it is reversed . The control of pain and temperature, maintenance of nutritional status, wounds repair, and fluid homeostasis maintenance, only reduces the afferent stimuli of the catabolic response, attenuating it; exogenous glucose can only reduce the obligatory nitrogen loss by decreasing the amplitude of gluconeogenesis. The hypermetabolic response in fact lasts until healing has occurred, infections and glycaemia are controlled, and nutrition adequately maintained.[81–90] The metaphysical aim of this phase is to increase cardiovascular function, preserve fluids, and increase the supply of substrates following an increase of demand. The flow-catabolic phase of blunt trauma without hemorrhage is very similar to the hyperdynamic reversible phase of septic shock with increased metabolism and temperature, and increased oxygen consumption in survivors, being both caused by a systemic inflammatory response.
A restorative anabolic-flow phase occurs when the catabolic phase has stopped, or has been terminated, and the patient can finally regain weight and energy. It is characterized by proteins synthesis and storage with a positive nitrogen balance. Nutrition from a tamponading-damage control role assumes now a rehabilitating and muscle energy building function.
In simple words, the three phases could well be described as summarized in a temporary “blackout phase” or “impact phase,” a “stress phase” and a “recovery phase.”
Trauma in general, as a bodily injury by physical, chemical, or mechanical causes with localized and systemic effects, is the only insult to have an ebb phase. Sepsis and other inflammatory do not have it and start directly on the flow-catabolic phase. Significantly, the hyperdynamic response to sepsis is very similar to the catabolic-flow phase.
The subdivision in Ebb and flow-catabolic phase is in fact arguable as both moments are indissolubly linked and consequential with a consecutio temporis et causae between the two periods, where the flow-catabolic phase is an obligatory rebound amplification of the impact phase with the insult. The ebb phase is nowadays tamponated by analgesia, fluids, and prima causa control or elimination. Therefore, it lasts practically until the initial therapeutic manouvres are effectuated. The lapse between Ebb and flow-catabolic phases is relevant in that the shorter the time-gap, the sicker or critical is the patient: when is too short or almost synchronous, like for example in the PTIR to severe massive multiple organs blunt trauma, the situation is unexceptionally unmanageable or controllable, and invariably fatal; if longer gap, the more chances of survival and successful intervention as the results of early intervention and damage control approaches show. Massive brain damage or coning and thoracic aorta detachment or dissection, or heart rupture, kill on the spot as fast as a severe PTIR from blunt trauma or from massive extensive thermal injury by chemicals, radiations or burns, and are practically unsalvageable too. The significance of the metabolic-cellular response is in the modulation of the reaction to the insult, in predisposing to complications and in needing specific nutritional requirement in the anabolic post-trauma/ post-operative phase.[88–90]
Human organisms, likewise animals and plants, are obligate aerobic organisms and temporary fallible biological systems created to live a temporary lifespan and reproduce species continuously. Without intervening external factors or genetic errors, each organism has a precise lifespan. Life and reality however, due to the “vertical perspective” of our caducity, fallibility and temporality and the “horizontal perspective” depending on space and earthly resources coordinates, inevitably and in the almost totality of cases, except few centenaries dying as for the end of the biological cycle, ends the life cycle much earlier than its maximal potential lifespan. Body reacts as far as to a certain point to internal or insults attacking physiological homeostasis, according to each physiological reserve and insult severity; not being built though to last forever or to contain all types and severity of insults the body defense mechanisms compensate and tamponade the insult up to a certain point following which give in if the insult is stronger or unstoppable. The common denominator of exitus, whether natural or pathological, is failure to produce energy for essential life processes, contained in the ATP molecule bonds. Pathways to exitus are therefore essentially one and the same. Microcirculation and cellular microcosm is where everything starts, where the will and thrust of and mystery of living begins, and ends, and to which the rest of the body-systems are functional. What moves the biological soul and life primum movens is and remains a mystery, and mystery by definition is beyond human comprehension. Energy needs oxygen and substrates, ie, perfusion to be produced. Mechanisms of critical illness therefore can be categorized in the ones where perfusion is scarce and in the ones where perfusion is normal or even increased but maldistributed. Once cells do not get enough energy for themselves produce some, death occurs. Death in shock is heralded by irreversible functional loss of the arterioles and/of the cellular system.
Source of Support: Nil
Conflict of Interest: None declared.
|1.||Rutherford RB,Balis JV,Trows RS,Graves GM. Comparison of hemodynamic and regional blood flow at equivalent stages of endotoxin and hemorrhagic shockJ TraumaYear: 19761688697825657|
|2.||McMillen MA,Huribal M,Sumpio B. Common pathway of endothelial-leukocyte interaction in shock, ischemia, and reperfusionAm J SurgYear: 1993166557628238752|
|3.||Fink MP. Bench-to-bedside review: Cytopathic hypoxiaCrit CareYear: 20026491912493070|
|4.||Ullian ME. The role of corticosteroids in the regulation of vascular toneCardiovasc ResYear: 199941556410325953|
|5.||Bonanno F. Extending damage control philosophy to non-haemorrhagic situations: Implications for a reclassification of shock statesANZ J SurgYear: 200878634718796014|
|6.||Boffard KD. Boffard KDResuscitative physiologyManual of Definitive Trauma CareYear: 2003LondonArnold publisher738|
|7.||Weil MH,Shubin H. Proposed reclassification of shock states with special reference to distributive defectsAdv Exp Med BiolYear: 19712313235164840|
|8.||Ince C,Sinaappel M. Microcirculatory oxygenation and shunting in sepsis and shockCrit Care MedYear: 19992713697710446833|
|9.||Ince C. The microcirculation is the motor of sepsisCrit CareYear: 20059Suppl 4S13916168069|
|10.||Ellis CG,Jagger J,Sharpe M. The microcirculation as a functional systemCrit CareYear: 20059Suppl 4S3816168072|
|11.||Vincent JL,De Backer D. Microvascular dysfunction as cause of organ dysfunction in severe sepsisCrit CareYear: 20059Suppl 4S91216168075|
|12.||Fink MP. Bench-to-bedside review: Cytopathic hypoxiaCrit CareYear: 20026491912493070|
|13.||Kilic YA,Yorganci K,Sayek I. Visualizing multiple organ failure: A method for analyzing temporal and dynamic relations between failing systems and interventionsCrit CareYear: 20071141717631034|
|14.||Saliba S,Kilic YA,Uranues S. Chaotic nature of sepsis and multiple organ failure cannot be explained by linear statistical methodsCrit CareYear: 20081241718439320|
|15.||Freitas FG,Salomao R,Tereran N,Mazza BF,Assunção M,Jackiu M,et al. The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shockClinics (Sao Paolo)Year: 2008644838|
|16.||Nevière R,Mathieu D,Chagnon JL,Lebleu N,Millien JP,Wattel F. Skeletal muscle microvascular blood flow and oxygen transport in patients with severe sepsisAm J Respir Crit Care MedYear: 199615319158542115|
|17.||Humer MF,Phang PT,Friesen BP,Allard MF,Goddard CM,Walley KR. Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigsJ Appl PhysiolYear: 1996818959048872661|
|18.||Samsel RW,Nelson DP,Sanders WM,Wood LD,Schumacker PT. Effect of endotoxin on systemic and skeletal muscle O 2 extractionJ Appl PhysiolYear: 1988651377823182506|
|19.||Anning PB,Sair M,Winlove CP,Evans TW. Abnormal tissue oxygenation and cardiovascular changes in endotoxemiaAm J Respir Crit Care MedYear: 19991591710510351908|
|20.||Dellinger RP,Carlet JM,Masur H,Gerlach H,Calandra T,Cohen J,et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shockIntensive Care MedYear: 2004305365514997291|
|21.||Dellinger RP,Levy MM,Carlet JM,Bion J,Parker MM,Jaeschke R,et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2008Intensive Care MedYear: 200834176018058085|
|22.||Lam C,Tyml K,Martin C,Sibbald W. Microvascular perfusion is impaired in a rat model of normotensive sepsisJ Clin InvestYear: 1994942077837962554|
|23.||Ellis CG,Wrigley SM,Groom AC. Heterogeneity of red blood cell perfusion in capillary networks supplied by a single arteriole in resting skeletal muscleCirc ResYear: 199475357688033345|
|24.||Nakajima Y,Baudry N,Duranteau J,Vicaut E. Microcirculation in intestinal villi: A comparison between hemorrhagic and endotoxin shockAm J Respir Crit Care MedYear: 200116415263011704607|
|25.||Ellis CG,Bateman RM,Sharpe MD,Sibbald WJ,Gill R. Effect of a maldistribution of microvascular blood flow on capillary O 2 extraction in sepsisAm J Physiol Heart Circ PhysiolYear: 2002282H1566411748059|
|26.||Bone RC,Balk RA,Cerra FB,Dellinger RP,Fein AM,Knaus WA,et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference CommitteeAmerican College of Chest Physicians/Society of Critical Care MedicineYear: 19921001164455|
|27.||Levy MM,Fink MP,Marshall JC,Abraham E,Angus D,Cook D,et al. 2001 SCCM/ESICM/ACCP/ATS/SIS: International sepsis definitions conferenceIntensive Care MedYear: 200329530812664219|
|28.||Baue AE. MOF, MODS, and SIRS: What is in a name or in an acronym?ShockYear: 2006264384917047513|
|29.||Bone RC,Balk RA,Cerra FB,Dellinger RP,Fein AM,Knaus WA,et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992ChestYear: 20091365 Supple2820162763|
|30.||Rivers E,Nguyen B,Havstad S,Ressler J,Muzzin A,Knoblich B,et al. Early goal-directed therapy in the treatment of severe sepsis and septic shockN Engl J MedYear: 200134513687711794169|
|31.||Rackow EC,Kaufmann BS,Falk JL,Astiz ME,Weil MH. Hemodynamic response to fluid repletion in patients with septic shock: Evidence for early depression of cardiac performanceCirc ShockYear: 19872211223608103|
|32.||Schumacker PT,Samsel RW. Oxygen delivery and uptake by peripheral tissues: Physiology and pathophysiologyCrit Care ClinYear: 19895255692650817|
|33.||Walley KR. Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: TheoryJ Appl PhysiolYear: 199681885948872660|
|34.||Yang S,Cioffi WG,Bland KI,Chaudry IH,Wang P. Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsisJ TraumaYear: 1999477061210528605|
|35.||Samsel RW,Nelson DP,Sanders WM,Wood LD,Schumacker PT. Effect of endotoxin on systemic and skeletal muscle O 2 extractionJ Appl PhysiolYear: 1998651377823182506|
|36.||Anning PB,Sair M,Winlove CP,Evans TW. Abnormal tissue oxygenation and cardiovascular changes in endotoxemiaAm J Respir Crit Care MedYear: 19991591710510351908|
|37.||Lappin E,Ferguson AJ. Gram-positive toxic shock syndromesLancet Infect DisYear: 200992819019393958|
|38.||Warden GD. Burn shock resuscitationWorld J SurgYear: 19921616231290260|
|39.||Jeschke MG,Mlcak RP,Finnerty CC,Norbury WB,Gauglitz GG,Kulp GA,et al. Burn size determines the inflammatory and hypermetabolic responseCrit CareYear: 200711R9017716366|
|40.||Beger HG,Rau B,Mayer J,Pralle U. Natural course of acute pancreatitisWorld J SurgYear: 19972113058995067|
|41.||Mayer JM,Rau B,Gansauge F,Beger HG. Multiple organ failure in human acute pancreatitis is associated with increased local and systemic inflammatory mediatorsGastroenterologyYear: 2000118A673|
|42.||Lundberg AH,Eubanks JW 3rd,Henry J,Sabek O,Kotb M,Gaber L,et al. Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivoPancreasYear: 200021415110881931|
|43.||Makhijia R,Kingsnorth AN. Cytoline storm in acute pancreatitisJ Hepatobiliary Pancreat SurgYear: 200294011012483260|
|44.||Beger HG,Rau B,Isenmann R. Natural history of necrotizing pancreatitisPancreatologyYear: 200339310112774801|
|45.||Vonlaufen A,Apte MV,Imhof BA,Frossard JL. The role of inflammatory and parenchymal cells in acute pancreatitisJ PatholYear: 20072132394817893879|
|46.||Deitch EA. Simple intestinal obstruction causes bacterial translocation in manArch SurgYear: 19891246997012730322|
|47.||Better OS,Stein JH. Early management of shock and prophylaxis of acute renal failure in traumatic rhandomyolisisN Engl J MedYear: 199032282592407958|
|48.||Michaelson M. Crush injury and crush syndromeWorld J SurgYear: 1992168999031462627|
|49.||Malinoski DJ,Slater MS,Mullins RJ. Crush syndrome: A reviewCrit Care ClinYear: 2004201719214979336|
|50.||Siegemund M,Stegenga ME,Mathura K,van Bommel J,Ince C. Changes in the porcine microcirculation of the ileum after supra-mesenteric aortic cross-clampingIntensive Care MedYear: 199925Suppl 1S10|
|51.||Yassin MM,Harkin DW,Barros D’Sa AA,Halliday MI,Rowlands BJ. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunctionWorld J SurgYear: 2002261152111898044|
|52.||Yassin MM,Barros D’Sa AA,Parks G,Abdulkadir AS,Halliday I,Rowlands BJ. Mortality following lower limb ischemia-reperfusion: A systemic inflammatory response?World J SurgYear: 19962096178798348|
|53.||Kologlu M,Sayek I,Kologlu B,Onat D. Effect of persistently elevated intra-abdominal pressure on healing of colonic anastomosesAm J SurgYear: 1999178293710587186|
|54.||Kologlu M,Yorganci K,Renda N,Sayek I. Effect of local and remote ischemia-reperfusion injury on healing of colonic anastomosesSurgeryYear: 20001289910410876192|
|55.||Moss GS,Saletta JD. Traumatic shock in manN Engl J MedYear: 197429072464205153|
|56.||Holcroft JW. Dunphy JEShockCurrent Surgical Diagnosis and TreatmentYear: 19825th edLos AltosLange Medical Publication17281|
|57.||Hardaway RM. Traumatic shockMil MedYear: 2006171278916673737|
|58.||Keel M,Trentz O. Pathophysiology of polytraumaInjuryYear: 20053669170915910820|
|59.||Schroeder JE,Weiss YG,Mosheiff R. The current state in the evaluation and treatment of ARDS and SIRSInjuryYear: 200940Suppl 4S82919895958|
|60.||Tsukamoto T,Chanthaphavong S,Pape HC. Current theories on pathophysiology of multiple organ failure after traumaInjuryYear: 20104121619729158|
|61.||Peng J,Du B. Sepsis-related stress response: Known knowns, known unknowns, and unknown unknownsCrit CareYear: 20101417920670385|
|62.||Bernard GR,Artigas A,Brigham KL,Carlet J,Falke K,Hudson L,et al. Report of the American-European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes and clinical trials coordination. The Consensus CommitteeIntensive Care MedYear: 199420225328014293|
|63.||Khadaroo RG,Marshall JC. ARDS and the multiple organ dysfunction syndrome.Common mechanisms of a common systemic processCrit Care ClinYear: 2002181274111910726|
|64.||Hardaway RM. A brief overview of acute respiratory syndromeWorld J SurgYear: 20063018293516957822|
|65.||Simpson CR,Sheikh A. Adrenaline is first line treatment for the emergency treatment of anaphylaxisResuscitationYear: 201081641220413204|
|66.||Dewachter P,Mouton-Faivre C,Nace L,Longrois D,Mertes PM. Treatment of anaphylactic reaction in pre-hospital and in the emergency room: Literature reviewAnn Fr Anesth ReanimYear: 2007262182817254745|
|67.||Elbers PW,Ince C. Mechanisms of critical illness – classifying microcirculatory flow abnormalities in distributive shockCrit CareYear: 20061022116879732|
|68.||Wan S,LeClerc JL,Vincent JL. Inflammatory response to cardiopulmonary bypass: Mechanisms involved and possible therapeutic strategiesChestYear: 1997112676929315800|
|69.||Jung C,Figulla HR,Ferrari M. High frequency of organ failures during extracorporeal membrane oxygenation: Is the microcirculation the answer?Ann Thorac SurgYear: 201089345620103290|
|70.||Dondorp AM,Angus BJ,Chotivanich K,Silamut K,Ruangveerayuth R,Hardeman MR,et al. Red cell deformability as a predictor of anemia in severe falciparum malariaAm J Trop Med HygYear: 199960733710344643|
|71.||Tsai AG,Cabrales P,Winslow RM,Intaglietta M. Microvascular oxygen distribution in awake hamster window chamber model during hyperoxiaAm J Physiol Heart Circ PhysiolYear: 2003285H15374512805029|
|72.||Schwarte LA,Fournell A,van Bommel J,Ince C. Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigsJ Appl PhysiolYear: 2005981070515475597|
|73.||Ellsworth ML,Forrester T,Ellis CG,Dietrich HH. The erithrocyte as a regulator of vascular toneAm J PhysiolYear: 1995269H2155618594927|
|74.||Dietrich HH,Ellsworth ML,Sprague RS,Dacey RG Jr. Red blood cell regulation of microvascular tone through adenosine triphosphateAm J Physiol Heart Circ PhysiolYear: 2000278H1294810749727|
|75.||Jagger JE,Bateman RM,Ellsworth ML,Ellis CG. Role of erythrocyte in regulating local O2 delivery mediated by haemoglobin oxygenationAm J Physiol Heart Circ PhysiolYear: 2001280H2833911356642|
|76.||Wihlborg AK,Malmsjo M,Eyjolfsson A,Gustafsson R,Jacobson K,Erlinge D. Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factorBr J PharmacolYear: 20031381451812721100|
|77.||Machiedo GW,Zaets SB,Berezina TL,Xu DZ,Feketova E,Spolarics Z,et al. Trauma-hemorrhagic shock-induced red blood cell damage leads to decreased microcirculatory blood flowCrit Care MedYear: 20093710001019237910|
|78.||Musterman LD,Elbers PW,Ozdemir A,van Dongen EP,van Iterson M,Ince C. Withdrawing intra-aortic balloon-pump support paradoxically improves microvascular flowCrit CareYear: 201014R16120738876|
|79.||Caprio K,Condon MR,Deitch EA,Xu DZ,Feketova E,Machiedo GW. Alteration of alpha-spectrin ubiquitination after hemorrhagic shockAm J SurgYear: 2008196663918954599|
|80.||Cuthbertson DP. Post shock metabolic responseLancetYear: 1942143342|
|81.||O’Keefe SJ,Sender PM,James WP. Catabolic loss of body nitrogen in response to surgeryLancetYear: 19742103584138097|
|82.||Cuthberson DP. Alterations in metabolism following injury: Part IInjuryYear: 198011175896988332|
|83.||Clague MB,Keir MJ,Wright PD,Johnstone ID. The effect of nutrition and trauma on whole body protein metabolism in manClin Sci (Lond)Year: 198365165756861447|
|84.||Kinney JM,Elwyn DH. Protein metabolism in the traumatized patientActa Chir Scand SupplYear: 198552245563893004|
|85.||Stoner HB. Metabolism after trauma and sepsisCirc ShockYear: 19861975873521932|
|86.||Monk DN,Plank LD,Franch-Arcas G,Finn PJ,Streat SJ,Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt traumaAnn SurgYear: 19962233954058633918|
|87.||Plank LD,Connolly AB,Hill GL. Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitisAnn SurgYear: 1998228146589712558|
|88.||Plank LD,Hill GL. Sequential metabolic changes following induction of systemic inflammatory response in patients with severe sepsis or major blunt traumaWorld J SurgYear: 200024630810773114|
|89.||Christou NV,McLean AP,Meakins JL. Host defense in blunt trauma: Interrelation of kinetics of energy and depressed neutrophil function, nutritional status and sepsisJ TraumaYear: 198020833417420493|
|90.||Mlcak RP,Jeschke MG,Barrow RE,Herndon DN. The influence of age and gender on resting energy expenditure in severely burned childrenAnn SurgYear: 20062441213016794397|
Keywords: Multiple organs dysfunction, multiple organs failure, shock.
Previous Document: Cleistanthus collinus poisoning.
Next Document: Severe metabolic acidosis following assault chemical burn.