1.Overview
Hypovolemic shock refers to the pathophysiological process of reduced effective circulating blood volume and cardiac output, inadequate tissue perfusion, disrupted cellular metabolism and impaired function due to the loss of circulating volume caused by various reasons. In the past 30 years, the treatment of hypovolemic shock has made great progress, however, its clinical mortality rate is still high. The main causes of death in hypovolemic shock are tissue hypoperfusion and multiple organ dysfunction syndrome (MODS) caused by hemorrhage, infection and reperfusion injury. Currently, there is a lack of comprehensive epidemiological data on hypovolemic shock.
Traumatic blood loss is the most common cause of hypovolemic shock. According to the statistics of foreign countries, the death of hemorrhagic shock caused by trauma accounts for 10%-40% of the total number of trauma deaths. The main pathophysiological change of hypovolemic shock is the rapid decrease of effective circulating blood volume, which leads to tissue hypoperfusion, increased anaerobic metabolism, lactic acidosis, reperfusion injury and endotoxin translocation, and finally leads to MODS.
The final outcome of hypovolemic shock is related to tissue perfusion from the beginning to the end, therefore, the key to improve the success of its treatment is to remove the cause of shock as soon as possible and restore effective tissue perfusion as soon as possible, so as to improve the oxygen supply to tissue cells, re-establish the balance of oxygen supply and demand and restore normal cell function. This guideline aims to recommend consensus opinions on clinical diagnosis, monitoring and treatment according to the latest evidence-based medical advances in hypovolemic shock, in order to facilitate the standardized clinical management of hypovolemic shock.
2.Etiology and early diagnosis
The loss of circulating volume in hypovolemic shock includes overt loss and non-overt loss. Explicit loss refers to the loss of circulating volume to the outside of the body, blood loss is the typical explicit loss, such as trauma! Blood loss from major surgical procedures, peptic ulcers, ruptured esophageal varices and acute blood loss from postpartum hemorrhage and other diseases. Explicit loss can also be caused by vomiting, diarrhea, dehydration, diuresis, etc. Non-obvious volume loss refers to the loss of circulating volume outside the circulatory system, mainly extravasation of circulating volume or circulating volume into the body cavity and other ways of non-obvious extracorporeal loss.
The early diagnosis of hypovolemic shock is crucial to the prognosis. The traditional diagnosis is based on history, symptoms and signs, including mental status changes, clammy skin, decreased systolic blood pressure (<90mmHg or >40mmHg compared to basal blood pressure, 1mmHg=0.133Kpa) or decreased pulse pressure difference (<20mmHg), urine output <0.5mmHg/(Kg・h), heart rate >100/min, and central nervous system. Heart rate >100/min, central venous pressure (CVP) <5mmHg or pulmonary artery wedge pressure (PAWP) <8mmHg, and other indicators.
However, in recent years, the limitations of the traditional diagnostic criteria have been fully recognized. Oxygen metabolism and tissue perfusion indicators have been found to have more important reference values for the early diagnosis of hypovolemic shock. Studies have confirmed the importance of blood lactate and base deficiency in the monitoring and prognosis of hypovolemic shock. In addition, it has been pointed out that indicators such as volume per beat (SV), cardiac output (CO), oxygen delivery (DO2), oxygen consumption (VO2), gastric mucosal CO2 tension (PgCO2), and mixed venous oxygen saturation (SvO2) also have some degree of clinical significance in shock resuscitation, but further evidence-based medical evidence is needed to support them.
The occurrence and extent of hypovolemic shock depends on the amount and rate of blood volume loss in the body. The average estimated blood volume in adults is 7% of body weight (or 70ml/Kg), and a 70Kg person has about 5L of blood. Blood volume changes with age and physiological condition, and when the percentage of body weight is used as the reference index, the blood volume of senior people is less (about 6% of body weight), the blood volume of children is 8%-9% of body weight, and the estimated blood volume of newborns is 9%-10% of body weight.
Blood loss can be classified into four levels based on indicators such as blood loss. Massive blood loss can be defined as blood loss exceeding the estimated blood volume of the patient within 24h or blood loss exceeding half of the estimated blood volume within 3h.
3.Pathophysiology
Loss of effective circulating blood volume triggers a series of pathophysiological responses in various systems and organs of the body to preserve body fluids, maintain perfusion pressure, and ensure blood perfusion to vital organs such as the heart and brain. Hypovolemia leads to excitation of the sympathetic-adrenal axis, increased release of catecholamines and selective constriction of skin, muscle and visceral vessels.
The contraction of the arterial system increases total peripheral vascular resistance to raise blood pressure; the contraction of the precapillary sphincter leads to a decrease in intracapillary hydrostatic pressure, thereby promoting intertissue fluid return; and the contraction of the venous system drives blood to the central circulation, increasing the amount of blood returned to the heart. Catecholamine hormones increase myocardial contractility, increase heart rate, and increase cardiac output.
Hypovolemia excites the renin-angiotensin II-aldosterone system, which increases aldosterone secretion and stimulates pressure receptors to induce the secretion of antidiuretic hormone from the posterior pituitary gland, thus enhancing sodium and water reabsorption by the renal tubules, reducing urine and preserving body fluid.
These compensatory responses have potential risks while maintaining the relative stability of circulatory system function and ensuring blood perfusion to vital organs such as the heart and brain. These potential risks are that the compensatory mechanism makes the blood pressure drop in the course of shock relatively slow and insensitive, which leads to the early recognition and treatment of poor tissue perfusion in shock if the blood pressure drop is used as the criterion for determining shock;
At the same time, the protection of cardiac and cerebral blood supply by compensatory mechanisms is at the expense of blood supply to other organs, and sustained renal ischemia can lead to acute renal impairment, and gastrointestinal mucosal ischemia can induce bacterial and toxin translocation. Endotoxemia and ischemia-reperfusion injury can induce the release of a large number of inflammatory mediators into the blood, prompting the irreversible development of shock.
The body’s response to hypovolemic shock also involves metabolic, immune, and coagulation systems, which also have adverse effects on the subsequent course of the disease. Increased secretion of adrenocorticotropic hormones and prostaglandins and decreased secretion of prolactin can cause immune suppression and make the patient vulnerable to infection. Pathological processes such as ischemia and hypoxia and reperfusion injury lead to coagulation disorders with the possibility of developing diffuse intravascular coagulation.
Tissue cell hypoxia is the essence of shock. In shock, microcirculation is severely impaired, tissue hypoperfusion and cellular hypoxia, the aerobic oxidation of sugar is blocked, anaerobic enzymes are enhanced, adenosine triphosphate (ATP) production is significantly reduced, lactic acid production is significantly increased and tissue accumulation, resulting in lactic acidosis, which causes irreversible damage to tissue cells and vital organs until MODS occurs.
Recommendation: We should be alert to the hypoxia of tissue cells in the course of hypovolemic shock with normal vital signs (Grade E).
4.Tissue oxygen delivery and oxygen consumption
In hypovolemic shock, the effective circulating blood volume decreases, resulting in a decrease in cardiac output and thus a decrease in DO2. For hemorrhagic shock, the degree of DO2 decrease not only depends on cardiac output, but also is affected by the degree of hemoglobin decrease. There is no clear conclusion whether VO2 decreases in hypovolemic shock when DO2 decreases.
When DO2 decreases to a certain threshold, even if oxygen uptake increases significantly, the VO2 of tissues and organs can not meet the oxygen consumption. Therefore, increasing the partial pressure of oxygen through oxygen therapy should be effective in improving oxygen delivery.
Studies have been conducted in post-surgical high-risk patients and in severely traumatized patients with ultra-high oxygen delivery as a resuscitation goal, and the results have shown a reduction in surgical mortality. However, many studies have also shown that hyperoxia delivery does not reduce mortality when compared to normal oxygen delivery as a resuscitation goal. Kem et al. reviewed numerous studies and found that early resuscitation before the onset of organ damage reduced mortality and may be more effective in patients with more severe disease.
Recommendation 5: During early resuscitation of hypovolemic shock, improve oxygen delivery as early as possible before MODS occurs (Class C.).
5. Monitoring
Some monitoring can make correct and timely assessment and judgment on the condition and treatment response of patients in hypovolemic shock to help guide and adjust the treatment plan and improve the prognosis of patients in shock.
5.1 General clinical monitoring includes monitoring indicators such as skin temperature and color, heart rate, blood pressure, urine output and mental status. However, these indicators are often difficult to show significant changes in the early stages of shock. The severity of decreased skin temperature, skin pallor, and collapsed subcutaneous veins depends on the severity of the shock. However, these symptoms are not specific to hypovolemic shock.
Increased heart rate is usually one of the early diagnostic indicators of shock, but heart rate is not an indicator of the amount of blood loss, for example, younger patients can easily compensate for moderate blood loss by vasoconstriction and show only a mild increase in heart rate.
Changes in blood pressure need to be monitored closely and dynamically. In the early stages of shock, blood pressure may remain at or near normal due to compensatory vasoconstriction. Some studies support the maintenance of “permissive hypotension” in hemorrhagic shock with uncontrolled bleeding. However, there is no clear conclusion as to what standard of permissible hypotension should be maintained due to the lack of in-depth studies on the relationship between blood pressure levels and the tolerable time of the body. Some studies have suggested that maintaining a mean arterial pressure (MAP) of 60-8 mmHg is appropriate.
Urine volume is a good indicator of renal perfusion, which can indirectly reflect the circulatory status. When the urine volume <0.5ml/(Kg・h), fluid resuscitation should be continued. It is important to pay attention to the clinical situation of patients in shock without oliguria, such as hyperglycemia and osmotic diuresis caused by osmotically active substances such as contrast media. Temperature monitoring is also important, as some clinical studies have concluded that hypothermia is harmful and can cause myocardial dysfunction and arrhythmias, and can lead to severe coagulation dysfunction when the central body temperature is <34°C.
5.2 Invasive hemodynamic monitoring
5.2.1 MAP monitoring invasive arterial blood pressure (IBP) is 5~20 mmHg higher than non-invasive arterial blood pressure (NIBP). when the state of persistent hypotension, manometry is difficult to accurately reflect the actual aortic pressure, while manometry is more reliable and can ensure continuous observation of blood pressure and immediate changes. in addition, it can also provide access to arterial blood collection.
5.2.2CVP and PAWP monitoring CVP is the most commonly used and easily available monitoring index, similar in meaning to PAWP, for monitoring preload volume status and guiding rehydration, which helps to understand the body’s responsiveness to fluid resuscitation and adjust the treatment plan in a timely manner. This is to prevent preload overload due to excessive infusion. In recent years, more studies have shown that the correlation between CVP and PAWP is not as strong as that between CVP and cardiac preload, depending on a number of factors.
5.2.3 CO and SV monitoring in shock, CO and SV can be reduced to varying degrees. Continuous monitoring of CO and SV can help to determine the clinical effect of volume resuscitation and cardiac function status dynamically.
In addition to the above indicators, some current studies have shown that fluid management by monitoring systolic blood pressure variability (SPV), beat-to-beat volume variability (SVV), pulse pressure variability (PPV), extravascular lung water (EVLW), and total intrathoracic blood volume (ITBV) in patients in hemorrhagic shock may be more reliable and effective than traditional methods. For patients on positive pressure ventilation, the application of EVLW and ITBV may provide a better assessment of volume status.
It should be emphasized that the significance of the values obtained by any of the monitoring methods is relative, because the various hemodynamic parameters are often influenced by many factors. The value of a single indicator sometimes does not reflect the correct hemodynamic status, and a comprehensive assessment of hemodynamics must be emphasized. In the implementation of comprehensive assessment, the following three points should be noted: combined with symptoms and signs of comprehensive judgment; analysis of the dynamic changes in values; comprehensive assessment of multiple indicators.
Recommendation 6: Patients in hypovolemic shock require close hemodynamic monitoring and dynamic observation of its changes (level E).
Recommendation 7: For patients with persistent hypotension, invasive arterial blood pressure monitoring (Level E) should be used.
5.3 Oxygen metabolism monitoring The concept of impaired oxygen metabolism in shock represents a major advance in the understanding of shock. Advances in oxygen metabolism monitoring have changed the way shock is assessed, while shifting the treatment of shock from the previous narrowly defined adjustment of hemodynamic indices to the regulation of oxygen metabolic status. In addition, changes in clinical indicators such as heart rate and blood pressure after therapeutic intervention can stabilize before tissue perfusion and oxygenation improve.
Therefore, it is of great clinical significance to monitor and evaluate some systemic perfusion indicators (DO2, VO2, blood lactate, SVO2 or SCVO2, etc.) as well as local tissue perfusion indicators such as gastric intra-mucosal PH (Phi) and PgCO2, etc. in patients given hypovolemic shock.
5.3.1 Pulse oximetry (SpO2)2 mainly reflects the oxygenation status, and can express the tissue perfusion status to some extent. Patients in hypovolemic shock often have hypotension, inadequate perfusion in the distal extremities, reduced oxygen delivery capacity or administration of vasoactive drugs, which affect the accuracy of SpO2.
5.3.2 Arterial blood gas analysis can identify the nature of fluid acid-base disorders, correct acid-base balance and adjust ventilator parameters in a timely manner according to the results of arterial blood gas analysis. Base deficiency can indirectly reflect the level of blood lactate. When the tissue blood supply is insufficient due to shock, the alkaline deficit decreases, indicating the existence of lactic acidemia. The combination of base deficit and blood lactate is a good method to determine the tissue perfusion in shock.
5.3.3 Monitoring of DO2 and SVO2 DO2 and SVO2 can be good indicators to assess the effect of early resuscitation in hypovolemic shock, and dynamic monitoring is of great significance. However, the value of DO2 and SVO2 for guiding fluid resuscitation in hypovolemic shock lacks strong evidence-based medical evidence.
5.3.4 Arterial blood lactate monitoring is a highly sensitive indicator of tissue hypoxia, and increased arterial blood lactate often appears before other signs of shock. Continuous dynamic monitoring of arterial blood lactate and lactate clearance is important for early diagnosis of shock, determination of tissue hypoxia, guidance of fluid resuscitation and prognosis assessment. However, blood lactate concentration may not adequately reflect the oxygenation status of tissues in some special cases such as combined hepatic insufficiency.
Studies have shown that in patients with post-traumatic hemorrhagic shock, the initial level of blood lactate and the duration of hyperlactate correlate with the degree of organ dysfunction and mortality.
5.3.5 Monitoring of PHi and PgCO2 PHi and PgCO2 can reflect the blood perfusion and pathological damage of intestinal tissues, as well as the oxygenation status of systemic tissues, which are of clinical value in assessing the resuscitation effect and evaluating the oxygen metabolism within the mucosa of the gastrointestinal tract.
Recommendation 8: In patients with hypovolemic shock, blood lactate should be monitored as well as the level and duration of base deficiency (level C).
5.4 Laboratory monitoring
5.4.1 Blood count, hemoglobin (Hb) and erythrocyte pressure product (HCT) can be monitored dynamically to understand whether the blood is concentrated or diluted, which is a reference value for the diagnosis of hypovolemic shock and whether there is continued blood loss. Some studies have shown that a 10% decrease in HCT within 4h indicates active bleeding.
5.4.2 Electrolyte monitoring and renal function monitoring are important for understanding changes in the condition and guiding treatment.
5.4.3 Coagulation monitoring is important in the early stages of shock to monitor coagulation function and to select the appropriate volume resuscitation plan and fluid type. Routine coagulation monitoring includes platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) and D-dimer. In addition, thromboelastography (TEG) is also included.
6.Treatment
6.1 Etiological treatment The degree of tissue and organ damage caused by shock is directly related to the amount of volume loss and the duration of shock. If shock persists and tissue hypoxia cannot be relieved, the pathophysiological state of shock will be further aggravated. Therefore, correcting the cause of volume loss as soon as possible is the basic measure to treat hypovolemic shock. For patients with progressive blood loss requiring emergency surgery after trauma, several studies have shown that minimizing the time between trauma and definitive surgery improves the prognosis and survival rate.
Other studies have shown that training physicians on the 60-min time limit for initial emergency care significantly reduces the rate of death in patients with hemorrhagic shock. A retrospective analysis of a large sample found that the primary cause of trauma hemorrhage death in the operating room was delayed admission and should be avoided. “Further studies suggest that early surgical hemostasis is necessary in patients with hemorrhagic shock with a clear site of bleeding, and a retrospective controlled study of 271 cases suggests that early surgical hemostasis improves survival. In patients with hemorrhagic shock in whom the site of bleeding cannot be determined, further evaluation is important.
This is because early management can only be achieved with early detection and diagnosis. Current clinical studies suggest that in patients with multiple trauma and torso-based hemorrhagic shock, bedside ultrasound can identify the site of bleeding early and thus indicate the indication for surgery early; other studies have confirmed that the test has better specificity and sensitivity than bedside ultrasound.
6.2 Fluid resuscitation fluid resuscitation treatment can be selected from crystalloid solutions (e.g. saline and isotonic balanced salt solution) and colloid solutions (e.g. albumin and artificial colloid solution). Since 5% glucose solution is quickly distributed to the intracellular space, it is not recommended for fluid resuscitation therapy.
6.2.1 Crystalloids The crystalloids commonly used for fluid resuscitation therapy are saline and lactated Ringer’s solution. Under normal circumstances, after the infusion of crystalloid fluid, it will be redistributed inside and outside the blood vessels, and about 25% will be retained inside the blood vessels, while the remaining 75% will be distributed in the extravascular space. Therefore, if a large amount of crystalloid is used for resuscitation in hypovolemic shock, it may cause dilution of plasma protein and decrease of colloid osmotic pressure, and tissue edema may occur at the same time.
In addition, saline is characterized by isotonicity but high chlorine content, so a large infusion may cause hyperchloremic metabolic acidosis; lactic acid Ringer’s solution is characterized by electrolyte composition close to physiological and contains a small amount of lactic acid. In general, lactic acid can be rapidly metabolized in the liver, and its effect on the blood lactate level should be taken into consideration when infusing large amounts of lactic acid Ringer’s solution. The method of resuscitation with hypertonic salt solution originated in the 1980s. In general, the sodium content of hypertonic salt solution is 400-2400 mmol/l.
The hypertonic salt solutions studied in recent years include hypertonic salt dextran injection (7.5% + 6% dextran70), hypertonic salt injection (7.5%, 5% or 3.5% NaCl) and 11.2% sodium lactate, of which the first two are the most common. Meta-analysis showed that HSD was more efficient than HS and saline for volume expansion during shock resuscitation, however, there was no effect on mortality. To date, there is not enough evidence-based medical evidence to prove that hypertonic saline solution is more beneficial as a resuscitation fluid for hypovolemic shock.
It is generally accepted that hypertonic saline solution expands volume by allowing intracellular water to enter the circulation. It has been shown to improve myocardial contractility and dilate small precapillary arteries in the presence of hemorrhage. Other basic studies on its effects on microcirculation and inflammatory responses are ongoing, and a recent study in patients with traumatic hemorrhagic shock has provided preliminary evidence of the immunomodulatory effects of hypertonic salt solution.
In patients with craniocerebral injury, several studies have shown that hypertonic salt solutions may have a promising future because they can rapidly increase mean arterial pressure without exacerbating cerebral edema, but there is a lack of evidence-based medical evidence for the use of hypertonic salt solutions in craniocerebral injury on a large scale. It is generally believed that the main risk of hypertonicity and hypernatremia, and even demyelination as a result, is the main risk of hypertonic salt solution, but the incidence of such complications has been low in several studies.
6.2.2 Colloid fluids There are many different colloid fluids available, including albumin, hydroxyethyl starch, gelatin, dextran, and plasma. The main colloid fluids used in clinical resuscitation for hypovolemic shock are hydroxyethyl starch and albumin. Hydroxyethyl starch (HES) is a synthetic colloidal solution, the main component of different types of preparations is branched chain starch of different molecular mass, the most commonly used is 6% sodium chloride solution, its osmotic pressure is about 773.4Kpa (300mosm/L).
Natural starch is rapidly hydrolyzed by endogenous amylase, while hydroxyethylation can slow down this process and maintain its volume expansion effect for a longer period of time. It has been shown that the higher the average molecular mass, the higher the substitution level, the longer the residence time in the blood vessel, and the higher the volume expansion intensity, but the greater the impact on renal function and coagulation system.
In terms of safety, the effects on renal function, coagulation and possible allergic reactions should be taken into account, and there is a certain dose-related effect. There is a lack of large-scale randomized studies on the effect of HES on coagulation, and several small-scale studies have shown that those with small molecular masses and slightly smaller substitution levels, but with high C2/C6 ratios, may have less effect on coagulation.
Other artificial colloids currently in clinical use include gelatin and dextran, both of which can be used for volume resuscitation purposes. Due to the different physicochemical and physiological properties, they are slightly different from each other in terms of volume expansion intensity and maintenance time, while the concern is the same in terms of application safety.
Recommendation 12: When applying artificial colloids for resuscitation, attention should be paid to the safety of different artificial colloids (Level C).
Albumin is a natural plasma protein that constitutes 75% to 80% of the plasma colloid osmotic pressure in normal humans, and the molecular mass of albumin is about 66 to 69 KU. Currently, human albumin preparations are available in 4%, 5%, 10%, 20% and 25% concentrations. As a natural colloid, albumin constitutes a major component of normal plasma to maintain volume and colloid osmotic pressure, and is therefore often chosen for fluid resuscitation during volume resuscitation. However, albumin is expensive and has the potential risk of transmitting blood-borne diseases.
6.2.3 The main difference between colloidal and crystalloid solutions during resuscitation is that colloidal solutions have a certain colloidal osmotic pressure, and the in vivo distribution of colloidal and crystalloid solutions is also significantly different. Studies have shown that both crystalloid and colloid solutions can restore tissue perfusion to the same extent when titrated to the same level of filling pressure. Multiple meta-analyses have shown that the various colloidal and crystalloid resuscitation treatments do not show differential effects on patient morbidity and mortality in trauma, burn and post-surgical patients.
In particular, the analysis showed that although crystalloids required significantly higher volumes for resuscitation than colloids, the differences in incidence of pulmonary edema, length of stay, and 28-d mortality were not significant. The available colloidal solutions differ in terms of physicochemical properties and plasma half-life. To date, there is a lack of large-scale clinical studies on the selection of different artificial colloid solutions for fluid resuscitation in patients with hypovolemic shock.
In the late 20th century, some studies suggested that the use of albumin could increase morbidity and mortality. Two subsequent meta-analyses concluded that the use of albumin was beneficial in patients with hypoalbuminemia and reduced mortality. The study also showed that the rate of death was significantly higher in the albumin group than in the saline group in patients with combined craniocerebral trauma.
Compared with albumin, artificial colloidal solutions with high molecular mass have a longer intravascular residence time and may have a better volume expansion effect than albumin, but large-scale clinical studies comparing artificial colloidal solutions with albumin or crystalloids for hypovolemic shock resuscitation are lacking.
Recommendation 13: At present, there is insufficient evidence to suggest that there is a significant difference in the efficacy and safety of crystalloids versus colloids for resuscitation of hypovolemic shock fluids (Grade C).
6.2.4 The importance of intravenous access to resuscitation fluids: fluid resuscitation in hypovolemic shock is urgent, and the rate of infusion should be fast enough to rapidly replace lost fluids to improve tissue perfusion. Therefore, effective venous access must be established rapidly during emergency volume resuscitation. Central venous catheters and pulmonary artery catheters should be placed and used in a manner that does not interfere with volume resuscitation.
Recommendation 14: To ensure rapid fluid resuscitation, effective venous access must be established as soon as possible (Level E).
Volume loading test: It is generally accepted that the purpose of volume loading test is to analyze and determine the status of volume loading and cardiovascular response during infusion in order to both rapidly correct the existing volume deficit and minimize the risk of volume overload and possible cardiovascular adverse effects. The volumetric load test consists of four aspects: fluid selection, infusion rate selection, timing and target selection, and safety limitations.
The latter two aspects can be simply summarized as the responsiveness and tolerance of the body to volume loading. Volume loading test should be actively used for patients with unstable hemodynamic status in hypovolemic shock.
6.3 Transfusion therapy transfusion and transfusion of blood products in hypovolemic shock is widely used. In hemorrhagic shock, the main loss is blood, but, while replenishing blood and volume, not all blood cell components need to be replenished, and the replenishment of coagulation factors should also be taken into account” At the same time, it should be recognized that blood transfusion may also bring some adverse effects and even serious complications.
6.3.1 Blood transfusion should be considered when the hemoglobin drops to 70 g/L to ensure the oxygen supply to the tissues. For patients with active bleeding, the elderly, and those at risk of myocardial infarction, it is more reasonable to maintain a higher level of hemoglobin. Patients without active bleeding have an increase in hemoglobin of about 10 g/l and an increase in hematocrit of about 3% for each unit (200 ml of whole blood) of red blood cells transfused.
Blood transfusion can bring about adverse effects such as blood-borne diseases, immunosuppression, increased erythrocyte fragility, and secretion of pro-inflammatory and cytotoxic mediators by residual leukocytes. Data show that increased transfusion volume is an independent predictor of poor patient prognosis. Currently, the general clinical indication for transfusion is hemoglobin ≤70g/l.
6.3.2 Platelet transfusion is mainly used for patients with reduced platelet count or abnormal platelet function with bleeding tendency, and can be considered when the platelet count is <50×10^9/L or when platelet function is determined to be low. Combined transfusion of platelets and cold precipitation can significantly improve hemostasis in patients with coagulation abnormalities after massive transfusion.
6.3.3 The purpose of fresh frozen plasma transfusion is to supplement the shortage of clotting factors. Fresh frozen plasma contains fibrinogen and other clotting factors. Some studies have shown that most patients with hemorrhagic shock still have difficulty in correcting coagulation function after acidosis and hypothermia have been corrected during resuscitation. Therefore, the coagulation function should be actively improved at an early stage. When a large amount of blood loss transfusion of red blood cells at the same time should pay attention to the use of fresh frozen plasma.
6.3.4 Cold precipitation contains coagulation factors V, VIII, XII, fibrinogen, etc. It is suitable for diseases caused by deficiency of specific coagulation factors, perioperative liver transplantation and bleeding from esophageal varices in liver cirrhosis. Timely infusion of cold precipitation can increase the content of coagulation factors and fibrinogen and other coagulation substances in the blood circulation and shorten the clotting time for patients with coagulation abnormalities after massive blood transfusion! Correct coagulation abnormalities.
Recommendation 15: For patients with hemorrhagic shock with hemoglobin <70g/L, transfusion therapy should be considered (grade C).
Recommendation 16: In case of massive blood loss, coagulation factor supplementation should be paid attention to (Grade C).
6.4 Vasoactive drugs and positive inotropic agents are generally not routinely used in patients in hypovolemic shock, and studies have confirmed the risk of these drugs further aggravating organ perfusion deficits and hypoxia. Vasoactive drugs and orthotropic agents are usually considered only for severely hypotensive patients who remain hypotensive after adequate fluid resuscitation or before the start of fluid infusion.
6.4.1 Dopamine is a central and peripheral neurotransmitter and a biological precursor of norepinephrine. It acts on three receptors: vascular dopamine receptors, cardiac B12 receptors and vascular A2 receptors. 1~3ug/(kg/min) mainly acts on brain, kidney, and mesenteric vessels, causing vasodilation and increasing urine output; 2~10ug/(kg/min) mainly acts on B2 receptors, increasing cardiac output by enhancing myocardial contractility, and also increasing myocardial oxygen consumption; >10ug/(kg/min). When 10ug/(kg/min), it mainly acts on vascular α-receptor excitation and constricts blood vessels.
6.4.2 Dobutamine dobutamine as β1 and β2 receptor agonist can increase myocardial contractility and produce vasodilation and reduce afterload. Recent studies have shown that the use of dobutamine after major surgical procedures can reduce postoperative complications and shorten hospitalization days. If hypovolemic shock patients have low cardiac output despite adequate fluid resuscitation, dobutamine should be used to increase cardiac output. If hypotension is also present, a combination of vasoactive agents may be considered.
6.4.3 Norepinephrine, epinephrine, and neoflavine are used only in refractory shock. Their main effect is to increase peripheral resistance to raise blood pressure, but they also constrict coronary arteries to varying degrees, which may aggravate myocardial ischemia.
Recommendation 17: In patients with hypovolemic shock with persistent hypotension, vasoactive drugs (class E) may be used as an option in the presence of active volume resuscitation.
6.5 AcidosisDecreased effective circulation in hypovolemic shock can lead to inadequate tissue perfusion and produce metabolic acidosis, the severity of which correlates with the severity of the trauma and the duration of shock. In a prospective, multicenter study, reduced base deficit was significantly associated with hypotension, prolonged coagulation time, and high trauma scores. Changes in base deficiency may suggest the effectiveness of early intervention. One author analyzed retrospective mortality factors in 3791 trauma patients and found that 80% of patients with base deficiency and BE <-15 mmol/L had a 25% morbidity and mortality rate.
The correlation between lactate level and MODS and death rate was found that the death rate was 25% for those with normal lactate level in hypovolemic shock 24-48h and 86% for those without normalization in 48h, and the early persistent high lactate level was significantly correlated with the occurrence of MODS after trauma.
Rapid onset of metabolic acidosis may cause severe hypotension, cardiac arrhythmia and death. The clinical use of sodium bicarbonate can transiently improve acidosis in shock, but its routine use is not recommended. Studies have shown that the management of metabolic acidosis should focus on etiological management, volume resuscitation and other interventions, and that the acidotic state can be gradually corrected during the process of tissue perfusion recovery. Therefore, in the treatment of hemorrhagic shock, bicarbonate therapy is used only for emergencies or PH<7.20.
Recommendation 18: Correct metabolic acidosis, emphasizing active etiological management and volume resuscitation; routine use of sodium bicarbonate (level D) is not recommended.
6.6 Protection of intestinal mucosal barrier function In hemorrhagic shock, gastrointestinal mucosal hypoperfusion, ischemia and hypoxia occur earliest and most seriously. The barrier function of gastrointestinal mucosa is rapidly weakened, and the chance of transferring bacteria or endotoxin from the intestinal lumen to the outside of the intestinal lumen increases. This process, known as bacterial translocation or endotoxin translocation, can persist after resuscitation. In recent years, it is believed that the intestine is the central organ of stress, and the ischemia-reperfusion injury of intestinal mucosa is an unfavorable factor in the pathophysiological development of shock and trauma. Protecting the intestinal mucosal barrier function and reducing the translocation of bacteria and toxins are important elements in the treatment and research of hypovolemic shock.
6.7 Temperature control of severe hypovolemic shock is often accompanied by intractable hypothermia, severe acidosis, and coagulation disorders. Hemorrhagic shock combined with hypothermia is a serious clinical sign of the disease, and retrospective studies have shown that hypothermia is often accompanied by more blood loss and higher morbidity and mortality. Hypothermia (<35°C) can affect platelet function, reduce the activity of clotting factors, and affect fibrin formation. Hypothermia increases the risk of severe bleeding in trauma patients and is an independent risk factor for increased bleeding and mortality.
However, controlled hypothermia in patients with combined craniocerebral injury has shown some positive effects compared to normothermia, and meta-studies have shown that it reduces mortality and promotes neurological recovery in patients with craniocerebral injury. Another meta-analysis showed that controlled hypothermia did not reduce morbidity and mortality, but was beneficial for neurological recovery. Patients with hypovolemic shock combined with craniocerebral injury who have a GCS score of 4-7 at admission can benefit from controlled hypothermia, which should be started and maintained as soon as possible after trauma.
Recommendation 19: Patients in severe hypovolemic shock with hypothermia should be promptly rewarmed and maintained at a normal temperature (grade D).
7. Resuscitation endpoints and prognostic evaluation indicators
7.1 For the resuscitation of hypovolemic shock, improvement in mental status, slowing of heart rate, increase in blood pressure and increase in urine output were often considered as resuscitation goals. However, these indicators often do not truly reflect the effective improvement of tissue perfusion in shock under the effect of organism stress and drugs. It has been reported that up to 50%-85% of patients with hypovolemic shock still have tissue hypoperfusion after reaching the above mentioned indicators, and the persistence of this state may eventually lead to higher morbidity and mortality; therefore, the normalization of these traditional indicators cannot be used as the endpoint of resuscitation in the process of clinical resuscitation.
Recommendation 20: Traditional clinical indicators have some clinical significance in guiding the treatment of hypovolemic shock, however, they cannot be used as an endpoint goal for resuscitation (level D).
7.2 Oxygen delivery and oxygen consumption have been used as resuscitation targets for high-risk patients with trauma, including hypovolemic shock, with cardiac index >4.5 L/(min/m2), oxygen delivery >600 ml/(min/m2) and oxygen consumption >170 ml/(min/m2). However, some studies have shown that these targets do not reduce the morbidity and mortality of trauma patients, and it was found that the survival rate of patients who were treated after resuscitation to achieve supernormal oxygen delivery targets did not improve significantly compared to those who did not meet the targets.
However, some studies have also concluded that patients who have achieved these targets early in resuscitation have a significantly higher survival rate. Therefore, strictly speaking, this index can be used as a prognostic indicator rather than a resuscitation endpoint target.
7.32 SVO2The change in SVO2 reflects the systemic oxygen uptake, and theoretically expresses the balance of oxygen supply and oxygen uptake, which was used by River et al. as an indicator of resuscitation from infectious shock, resulting in a significant decrease in the morbidity and mortality rate. There is a lack of evidence on SVO2 in hypovolemic shock, and there is also a lack of data comparing SVO2 with lactate, DO2 and PHi as resuscitation endpoints.
7.4 Blood lactate blood lactate levels! duration is closely related to the prognosis of patients in hypovolemic shock, and persistently high levels of blood lactate (>4 mmol/L) are indicative of a poor prognosis. Blood lactate clearance is a better indicator of patient prognosis than blood lactate values alone. Normalization of lactate clearance as a resuscitation endpoint is better than MAP and urine output, and better than DO2, VO2, and CI.
Normalization of blood lactate concentration (≤2 mmol/l) is the criterion, and the return to normal blood lactate concentration (≤2 mmol/l) in the first 24 h of resuscitation is extremely critical. Patients whose blood lactate decreases to normal within this time have a significantly higher survival rate with the elimination of the etiology.
Recommendation 21: The time to normalization of arterial blood lactate and blood lactate clearance are closely related to the prognosis of patients in hypovolemic shock, and the assessment of resuscitation should refer to these two indicators (grade C).
7.5 Base deficiency Base deficiency can reflect the degree of systemic tissue acidosis. Base deficiency can be divided into: mild (-2~-5mmol/l), moderate (<-5~≥-15mmol/l), and severe (<-15mmol/l). The level of alkaline deficiency correlated with the amount of crystalloid and blood replenishment in the first 24 h after trauma, and increased alkaline deficiency was mostly associated with progressive bleeding. Patients with increased alkaline deficiency who appear to be stable should be carefully examined for progressive bleeding.
Several studies have shown a strong correlation between alkaline deficiency and patient prognosis, including a prospective, multicenter study that found that the lower the value of alkaline deficiency, the higher the incidence of MODS, death and coagulation disorders, and the longer the length of hospital stay.
Recommendation 22: The level of base deficiency is closely related to the prognosis and should be monitored dynamically during resuscitation (level)”
7.6 PHi and PgCO2PHi reflects the perfusion status of visceral or local tissues, has early warning significance for shock, and correlates with the prognosis of patients in hypovolemic shock. It has been demonstrated that PgCO2 is more reliable than PHi. When the gastric mucosa was ischemic, PgCO2>PaCO2, and the difference of P(g-a)CO2 was related to the degree of ischemia. normal value of PgCO2<6.5Kg, normal value of P(g-a)CO2<1.5Kpa, the larger the value of PgCO2 or P(g-a)CO2, the more serious the ischemia.
PHi resuscitation to >7.30 as an endpoint and time to reach this endpoint <24 h is similar to resuscitation with hyper normoxia delivery as an endpoint, but predicts patient death and MODS earlier and more accurately than oxygen delivery. However, a recent prospective, multicenter study found no significant differences in patient morbidity and mortality, incidence of MODS, duration of mechanical ventilation, or days in hospital between conventional treatment guided by gastric mucosal tonometry and treatment guided by gastric mucosal tonometry with maximal improvement in hypoperfusion and reperfusion injury.
7.7 Other skin, subcutaneous tissue and muscle vascular beds can be used to more directly measure perfusion at the local cellular level. New techniques such as transcutaneous or subcutaneous oxygen tension measurements, near-infrared spectroscopic analysis and the application of optical fibers to determine oxygen tension measurements have advanced resuscitation endpoints to the cellular and subcellular level. However, there is a lack of rapid and accurate evaluation results and large-scale clinical validation of the above techniques.
8.Resuscitation of hemorrhagic shock with uncontrolled bleeding
Hemorrhagic shock with uncontrolled bleeding is a special type of hypovolemic shock, commonly seen in severe trauma (penetrating injury, vascular injury, substantial organ injury, long bone and pelvic fracture, chest trauma, retroperitoneal hematoma, etc.), gastrointestinal bleeding, obstetrical and gynecological bleeding, etc. The main cause of death in patients with uncontrolled hemorrhagic shock is severe and sustained hypovolemic shock or even cardiac arrest due to massive bleeding.
A large number of basic studies have confirmed that early aggressive resuscitation in hemorrhagic shock with uncontrolled bleeding can cause dilutive coagulation dysfunction; blood pressure increases, the clot formed in the blood vessels is dislodged, resulting in rebleeding; excessive blood dilution, hemoglobin decreases, reducing tissue oxygen supply; complications and morbidity and mortality rates increase. Therefore, controlled fluid resuscitation (delayed resuscitation) is proposed, that is, small volume fluid resuscitation should be given before active bleeding is controlled to maintain perfusion and oxygen supply to vital organs within the short-term permissible hypotensive range and to avoid the side effects of early aggressive resuscitation.
Animal studies have shown that restrictive fluid resuscitation can reduce morbidity and mortality, rebleeding rates and complications.
One study compared the effects of immediate resuscitation and delayed resuscitation on morbidity and mortality and complications in trauma hypotensive patients (systolic blood pressure <90 mmHg) with torso penetrating injuries. A retrospective clinical study showed that the early resuscitation rate of patients with uncontrolled hemorrhagic shock was significantly higher than that of patients with delayed resuscitation on arrival at the hospital.
Another clinical study also found that maintaining systolic blood pressure at 70 mmHg or 100 mmHg during early resuscitation of active bleeding did not affect patient morbidity and mortality, and the lack of difference in outcome may be related to the small number of patients, the type of disease (49% for blunt contusions and 51% for penetrating injuries), the mild severity of disease, and the methodology of the study, which also achieved a mean systolic blood pressure of 100 mmHg in the restrictive resuscitation group. In addition, massive crystalloid resuscitation increases the incidence of secondary abdominal septal syndrome.
For hemorrhagic shock with non-traumatic uncontrolled bleeding, some studies have shown that in patients with hemorrhagic shock with gastrointestinal bleeding, the rebleeding rate was significantly increased in the early transfusion group. However, there is no clear conclusion as to whether early restrictive fluid resuscitation is appropriate for all types of hemorrhagic shock, how high blood pressure needs to be maintained, and how long it can last. However, regardless of the cause of hemorrhagic shock, the first principle of treatment must be to quickly stop the bleeding and eliminate the cause of blood loss.
For patients with craniocerebral injury, the appropriate perfusion pressure is the key to ensure the oxygen supply to the central nervous tissue. After craniocerebral injury, the intracranial pressure increases, and if the body blood pressure decreases at this time, the cerebral blood perfusion will be insufficient and secondary ischemic damage to brain tissue, further aggravating the craniocerebral injury. Therefore, it is generally believed that for patients with severe hemorrhagic shock combined with craniocerebral injury, early infusion is advisable to maintain blood pressure and, if necessary, combine with vasoactive drugs to maintain systolic blood pressure at normal levels to ensure cerebral perfusion pressure, rather than delaying resuscitation. Permissive hypotension should be used with caution in elderly patients and should also be considered contraindicated in patients with a history of hypertension.