Shock (pediatrics)

Shock is defined as a disproportion between the need and supply of oxygen to the tissues. It is a micro and/or macrocirculation disorder that leads to failure of tissue perfusion, oxygen consumption and energy metabolism of cells. Insufficient oxygen supply leads to a shift of aerobic metabolism to a less efficient anaerobic metabolism, lactic acidosis occurs. The Brain does not have the capacity for anaerobic metabolism, and that is why it is seriously affected when there is a lack of oxygen.

The most common form of shock in children is hypovolemic and septic shock.

As stated above, the measure of shock is perfusion impairment. The following table gives the answer to the question of which clinical condition can already be considered as shock.

Oxygen delivery (oxygen delivery, DO2)
Oxygen delivery (DO2) is directly proportional to cardiac output and the oxygen content in arterial blood (arterial oxygen content, CaO2). For pediatrics, we always choose indexed values, i.e. values related to the body surface.


 * DO2 (index) = CI x CaO2 x 10
 * CI = HR x SV
 * CaO2 = (Hb x 1.34 x SaO2) + (0.003 x PaO2)
 * CvO2 = (Hb x 1.34 x SvO2) + (0.003 x PvO2)
 * a - v DO2 = CaO2 - CvO2
 * DO2 = oxygen delivery, represents oxygen delivered by tissue per minute, reference values DO2 = 550-650 ml/min/m2
 * SV = stroke volume = pulse volume
 * HR = heart rate = heart rate
 * CI = cardiac index = cardiac index (this is cardiac output related to a unit of body surface area)
 * CaO2 = oxygen content in arterial blood, reference values CaO2 = 17 – 20 Jr.
 * CvO2 = oxygen content in mixed venous blood, reference values CvO2 = 12– 15 ml
 * SaO2 = saturation of arterial blood O2, it is reported as SaO2/100
 * SvO2 = saturation of mixed venous blood, it is given as SvO2/100
 * PaO2 = partial pressure of oxygen in arterial blood, it is given in torrs
 * PvO2 = partial pressure of oxygen in mixed venous blood, it is given in torr
 * a-v DO2 = arteriovenous oxygen content difference (oxygen content difference), reference values a-v DO2 = 3 – 5 ml/dl
 * Hb = hemoglobin, it is given in the amount of g/dl

Oxygen consumption (oxygen consumption, oxygen uptake, VO2)
The rate of O2 consumption is VO2 (oxygen consumption, oxygen uptake), reference values VO2 (index) = 120 – 200 ml/min /m2


 * VO2 (index) = CI x (CaO2 - CvO2) × 10

The basic task of the cardiopulmonary unit is to ensure the balance between DO2 and VO2. Equilibrium is determined by:
 * oxygen content in mixed venous blood CvO2
 * O2 extraction (oxygen extraction, O2ER), i.e. the ratio between the amount of consumed and delivered oxygen VO2 / DO2, which is expressed as a percentage. Normal extraction values are around 25%, but with significantly increased tissue demand or reduced perfusion, O2 extraction can rise to 50%. As part of the shock states, we try to keep the oxygen extraction below 30%.


 * O2ER = VO2 / DO2

Both CvO2 and O2ER depend on the mixed venous blood saturation values of SvO2 and cardiac CO output. CO/CI depends on heart rate value and stroke volume (the latter is determined by preload, afterload and contractility). Increasing heart rate, improving myocardial contractility and relaxation in diastole, optimizing preload and afterload increase CO/CI. Oxygen carrying capacity can be improved by optimizing hematocrit. For critically ill children, but in a stable condition, we consider a hemoglobin value of 70 g/l as the borderline for transfusion. By improving all these parameters, DO2 can be increased. In some specific situations (fever, high flow stage sepsis, trauma, thyrotoxicosis) metabolic needs can exceed even normal DO2.

With insufficient supply of O2, some cells can cover their energy needs by anaerobic glycolysis, i.e. by converting glucose into lactic acid. However, the energy efficiency is negligible (2 ATP per glucose compared to 36 ATP in oxidative combustion). The dissociation of lactic acid into H+ and lactate then leads to the development of MAC. The lack of energy first causes the limitation of cell function and finally their irreversible damage. Likewise, shock is a condition caused by a severe and extensive reduction in effective tissue perfusion leading first to reversible, then irreversible cell damage. Effective tissue perfusion can be reduced globally, i.e. by reducing the minute cardiac output or increasing inefficient regional perfusion based on blood flow distribution disorders or substrate utilization disorders at the cellular level.

Factors that determine the effectiveness of tissue perfusion can understandably cause shock even if they are severely affected in isolation. In most cases, especially in later forms of shock, these are manifestations of multifactorial damage. Determinants of effective tissue perfusion can be classified into 4 main categories:
 * 1) quantities affecting the performance of the heart muscle;
 * 2) effective blood volume;
 * 3) factors affecting vascular resistance and permeability (and thus the distribution of circulating blood volume);
 * 4) factors affecting the availability of oxygen at the cellular level.

From a practical point of view, it should be noted that shock can be present with normal, decreased or increased cardiac output, with normal, decreased or increased BP.

In children, at first it is often hypodynamic shock = low flow with reduced CO/CI and, conversely, high peripheral systemic resistance (the exception is the initial phase of septic shock, hepatic failure, thyrotoxic crisis, etc.).

Circulation and ventilation
It is necessary to monitor the heart rate, blood pressure invasively – IBP (monitor MAP and perfusion pressure values), via CVK then CVP and SvcO2, continuous ECG and pulse oximetry monitoring.

Indications for the introduction of a Swan-Ganz catheter are extremely rare in pediatrics (severe form ARDS using PEEP > 10 cmH2O, monitoring of patients after some corrections [[Congenital heart defects|VVV heart] ]). A Swan-Ganz catheter is also considered in patients who remain in shock despite pressure-correcting therapy but SvcO2 is < 70%. Due to the invasiveness and risk of introducing a pulmonary catheter, semi-invasive options for measuring cardiac output are clearly preferred today, e.g. the PiCCO method, which also enables the determination and calculation of other hemodynamically important parameters.

We intermittently check blood gases and ABR from arterial blood (arterial line). The advantage is etCO2 monitoring during UPV, which allows to reduce the frequency of blood sampling.

As part of the ventilation, we then monitor the respiratory frequency and, when applying UPV, a number of parameters depending on the use of pressure or volume ventilation. But we always follow PFi = pO2 / FiO2, oxygenation index = (FiO2x Pmaw) / pO 2, lung compliance and resistance, Vd/Vt parameter.

Standard examinations are chest X-ray, echocardiography and ECG (12-lead recording). In the intensive care environment, this is the so-called bed-side monitoring.

Consciousness
Within the framework of the shock state, the "impairment of consciousness" can be expressed in many different ways, both qualitatively and quantitatively. Classification scales are used for objectification: Beneš score and above all Glasgow coma scale (GCS).

We monitor the state of the pupils, stem reflexes (nasopalpebral, corneal), the state of muscle tone, possibly complete neurological monitoring as needed. If the condition requires "absolute" monitoring of CNS function, we use continuous EEG, intraparenchymatous measurement of intracranial pressure (ICP), multimodal intraparenchymatous sensors (monitor pH, pCO2 and pO2), monitoring of blood saturation in the jugular bulb SvjO2, transcranial Doppler ultrasonography, spectroscopy using near infrared radiation (near infrared spectroscopy = NIRS), ev. microdialysis. When imaging methods are indicated, we prefer CT and MRI.

Laboratory
As part of biochemical monitoring we investigate: KO + diff. (possibly also blood group), creatinine, urea, iontogram, liver tests, S-amylase, glycemia, albumin, lactate, S-osmolality and hemocoagulation.

We are interested in chemistry and sediment, urinary osmolality, waste ions, creatinine and urea from urine examination. Hyperosmolar urine with low natriuresis is demonstrated in the case of a deficit of effective circulating volume or, conversely, hypoosmolar urine with high natriuresis in acute renal failure (shock kidney). Evidence of microalbuminuria is a marker of endothelial damage. A fundamental examination before starting ev. antibiotic therapy is collection by cultures (blood culture, urine, CSF, purulent collections - pleural exudate, joint effusion, puncture of abscess, etc.). From a general point of view, we demonstrate a lactate MAC, when lactate is > 2 mmol/l, a widening of the anion gap and a decrease of bicarbonate. Unfortunately, the specificity of hyperlactacidemia is not high, a simple lactate value does not reveal regional perfusion disorders, the lactate level also depends on hepatic production. Considering these aspects, the modern method gastric tonometry appears to be more advantageous for assessing organ perfusion.

The value of "glycemia" can be increased (more often) or decreased. Hyperglycemia is caused by insulin receptor resistance to insulin.

Changes in serum osmolality and blood biochemistry are dependent on the precipitating cause of the shock state. A sudden decrease in leukocytes can indicate a violation of the integrity of the vascular wall. The finding of hypophosphatemia indicates a major disorder of intracellular metabolism, as phosphorus is a valuable intracellular ion.

It is essential to monitor "diuresis", in the case of a shock state always an hourly diuresis with a 6-hour fluid balance. This means the unconditional insertion of a urinary catheter. A good diuresis is an excellent reflection of the adequacy of organ perfusion. But beware – sufficient diuresis can be misleading in the polyuric type of acute renal failure. We also monitor peripheral and central body temperature, as well as inflammatory markers (especially CRP and procalcitonin) as part of comprehensive diagnostics.

Gastrointestinal tract
We always insert a Nasogastric tube (NGS). At first, we use it to decompress the GIT and suction the stomach contents to prevent possible aspiration. The implementation of NGS is absolutely essential in patients with suspected sudden abdominal events where we must not give anything p.o., or in patients after drowning where there is a high risk of aspiration.

Gradually, NGS is used as a way of enteral nutrition. In the case of gastric atony, it is necessary to implement enteral nutrition via a nasojejunal tube (in this case, bolus feeding can no longer be used, but continuous feeding - usually 21 hours with a three-hour break). The basis is the monitoring of peristalsis, evaluation of residues in the probe, registration of the number and nature of stools. Stool examination is used for culture, proof of occult bleeding or proof of clostridial antigen and toxin (Clostridium difficile). The most important imaging examination is undoubtedly sonography.

As part of liver function, we monitor complete liver tests (bilirubin direct and indirect, transaminases, GMT, ALP, LDH, cholinesterase), ammonia, coagulation (especially Quick and fibrinogen), albumin, glycemia and urea.

The modern method of gastric tonometry is suitable for assessing organ perfusion. Its advantage is the detection of regional hypoperfusion affecting the digestive tract (as a prototype of splanchnic circulation), the advantage is also continuous measurement. However, this method assumes that hypoperfusion of the splanchnic region will precede systemic perfusion. The disadvantage of this method is its relative invasiveness.

Methods monitoring regional perfusion
The values of serum lactate or the values defining MAC are a reflection of the global situation and, moreover, their results are mostly limited by the collection of venous blood. Methods defining regional perfusion and at the same time minimally invasive are in the foreground: gastric tonometry, NIRS (near-infrared spectroscopy), rectal tonometry, sublingual capnometry. All these methods are in the research stage and their routine use is not part of the article. recommended.

Patient Assurance
The basic step in approaching a patient in a state of shock is to ensure the patency of the airways, administer 100% oxygen, ventilate with an ambuvac mask if necessary or intubate the patient and, if possible, start UPV as soon as possible. . Regardless of the etiology of the shock state, quick decisions should always be made for ventilatory and circulatory support. The introduction of UPV in shock states is not generally applied only on the basis of a diagnosis of global respiratory insufficiency, but hypermetabolism, hyperkinetic circulation, resistant metabolic acidosis, impaired consciousness and extreme work of breathing may lead to a decision on adequate provision of the child. We therefore indicate early intubation and UPV (in general, sooner rather than later). It is necessary not to leave the child in respiratory distress for too long. UPV allows redistribution of cardiac output from the respiratory muscle area toward vital organs, plus positive pressure UPV reduces afterload and can increase stroke volume. The disadvantage of UPV in patients with hypovolemia is that during positive pressure ventilation preload continues to decrease and hypotension can manifest.

If the anamnesis or clinical examination indicates pneumothorax or hemothorax, we will consider the urgency of performing a pleural puncture. At the same time, it is necessary to ensure circulation, i.e. ensure intravenous (2 IV lines are ideal) or intraosseous access. In neonates, we prefer umbilical vein cannulation. For children > 6 years old, an alternative is when it is impossible to provide i.v. entry cannulation of the central venous course, if an experienced doctor who controls the technique is available and the patient is in an environment where complications arising from the cannulation can be dealt with urgently. After the basic securing of entry into the circulation, the next step is the elective securing of the CVK and arterial line. The goal is to achieve CI 3.3–6 l/min/m2 and oxygen consumption VO2 (oxygen consumption) > 200 ml/min/m 2 /vul>. The recommended Hb value for shock states is approx. 100 g/l, Ht 0.30–0.40.

Inoconstriction and inodilation treatment
The basic goal of the administration of these substances is to increase tissue perfusion and maintain perfusion gradients, however, a prerequisite for their effect is sufficient filling of the vascular bed. The administration of inodilating substances in a hypovolemic patient can cause serious complications resulting from hypotension or tachyarrhythmia. Administration of inoconstrictive substances is not effective in normal doses. Vasopressors should be titrated according to perfusion pressure or systemic vascular resistance so that diuresis and physiologic creatinine clearance are optimal.

It should be noted that if the shock is complicated by myocardialial dysfunction, then preparations with a positive inotropic effect (increasing contractility) can reduce preload and afterload, improve myocardial oxygen supply by increasing coronary perfusion pressure. Coronary flow is also improved by lengthening the diastolic phase while lowering the heart rate. However, if a drug with a positive inotropic effect is administered to a patient with normal cardiac contractility, the result may be increased myocardial oxygen consumption.

We also ensure normal reactivity of the myocardium and vascular system by maintaining normal acid-base ratios and electrolyte levels, especially potassiumu, magnesiumu and calciumu. Inoconstrictors or inodilators are usually administered with a linear dispenser. When dealing with circulatory complications in critically ill patients, we use one or two substances, exceptionally a larger number. The effect on individual receptors is in some cases dose-dependent (e.g. dopamine, adrenaline) and their introduction into the systemic circulation should be completely separated from other substances. We preferably use multi-channel central venous catheters for this purpose. Catecholamine solutions must be protected from light and we require intra-arterial BP measurement when administered. Administration into peripheral veins causes early reactive inflammation. Only dobutamine, other catecholamines can only be administered into the peripheral watercourse for a short time and with maximum dilution.

From a clinical point of view, it is possible to divide the group of inotropic substances into substances that are inoconstrictive (noradrenaline, adrenaline, dopamine) and substances that are inodilatory (dopexamine, dobutamine, isopreterenol). A specific group of inotropic substances are phosphodiesterase III blockers (PDE III) = inodilators in the narrower sense of the word. Catecholamines stimulate α-1, α-2, β-1, β-2 and dopaminergic = ɗ-receptors and lead to an increase in cAMP (cyclic adenosine monophosphate), PDE III inhibitors increase cAMP by preventing its degradation inside cells.

Mechanism of action
Adrenergic receptors are represented by 8 gene subtypes, but from a practical point of view we distinguish α-1, α-2, β-1, β-2 and ɗ-1 and ɗ-2 receptors.

Both β-1 and β-2 receptors are located in the ventricular myocardium muscle and the atrial muscle. In addition, β-2 receptors are located on the presynaptic endings of sympathetic nerves and stimulate the release of neurotransmitters. In the smooth muscle of blood vessels, activation of β-2 receptors leads to vasodilation, in the smooth muscle of bronchi to bronchodilation (through the mechanism of smooth muscle relaxation). β-2 receptors in the SA node are responsible for the positive chronotropic effect. β-1 stimulation of the myocardium increases not only inotropy (force of contraction), but also varying degrees of chronotropy (increased heart rate), dromotropy (increased conduction velocity) and bathmotropy (increase in irritability).

α-1 receptors are mainly found in the smooth muscle of blood vessels, where they cause vasoconstriction. However, α-1 receptors are also found in the muscle of the myocardium. Their irritation has a positive inotropic effect, but does not affect the heart rate. α receptors were originally differentiated with respect to their location on nerve endings. The postsynaptic receptor was designated as α-1 and the presynaptic receptor as α-2. Stimulation of the α-1 receptor leads to the contraction of smooth muscle, while stimulation of the α-2 receptor inhibits the release of noradrenaline from presynaptic granules, thus promoting vasodilation.

Dopaminergic (delta) receptors are divided like others into postsynaptic ɗ-1 and presynaptic ɗ-2. ɗ-1 receptors are located in the smooth muscle of renal, splanchnic, coronary and cerebral vessels. Their activation leads to vasodilation. ɗ-2 receptors inhibit the release of noradrenaline from sympathetic endings.

The mechanism of action of phosphodiesterase blockers is based on the fact that normally cAMP is inactivated by phosphodiesterase, which causes its conversion to AMP. Inhibition of phosphodiesterase increases cAMP concentration and enhances β-receptor mediated activity.

Disorders of receptor function
As part of the receptor disorder, the mechanism of reducing the sensitivity of receptors is best described on the principle of agonist-mediated desensitization. Within seconds to minutes after agonist binding to the receptor, uncoupling may occur due to receptor phosphorylation (phosphorylation involves multiple mechanisms). In addition to agonist-mediated desensitization, there are other factors involved in so-called down-regulation: endotoxin, TNF, congestive heart failure. Another mechanism of down-regulation of receptors is their sequestration inside target cells and their subsequent degradation.

Adrenaline
Adrenaline is produced in the adrenal medulla (tyrosine -> DOPA -> dopamine -> noradrenaline -> adrenaline). Adrenaline is a potent, directly acting α-1, β-1 and β-2 receptor agonist.

Adrenaline in low concentrations first affects β-2 receptors. It potentiates the activity of the SA node, increases the heart rate, helps vasodilation, i.e. a decrease in SVRI and decreases diastolic blood pressure. A decrease in SVRI further increases the direct chronotropic effect of adrenaline. Unfortunately, the increased consumption of oxygen by the myocardium is a disproportionate increase in inotropy and thus decreases myocardial performance. As the concentration increases, the α-1, β-1 component rapidly enters. Stimulation of α-1 receptors leads to an increase in SVRI (significantly in the area of the splanchnic) and at the same time pulmonary vascular resistance. High doses of adrenaline or its use in patients with myocarditis or infarction can lead to the development of severe atrial and ventricular dysrhythmias.

In practice, the combination of the β-2 effect, which lowers diastolic pressure, and the α-1 effect, which increases systolic pressure, increases the pulse pressure value.

During stress, when a large amount of adrenaline is flushed out, receptors can be desensitized very quickly, even before exogenous adrenaline administration begins.

Adrenaline is intended for the treatment of shock in connection with myocardial dysfunction, especially in patients after successful cardiopulmonary resuscitation or after a hypoxic-ischemic insult. In septic patients, where there was no improvement in the condition after volume expansion, continuous infusion of adrenaline can be beneficial. Adrenaline is most useful in conditions with hypotension, low CI and high SVRI (cold shock = low flow). At low doses of 0.005–0.1 μg/kg/min, SVRI slightly decreases, but heart rate, blood pressure, and cardiac output increase. In medium doses of 0.1–1.0 μg/kg/min. α-1 adrenergic activity begins to predominate and the further increase in CO balances the still persistent vasodilation (induced by the activation of β-2 receptors), which, as already mentioned, leads to a decrease in diastolic pressure. In very high doses (> 1–2 μg/kg/min.), vasoconstriction by activation of α-1 receptors predominates, splanchnic perfusion is significantly reduced, afterload increases, and myocardial function may decrease with elevation of serum [[lactate] ]at.

As part of cardiopulmonary resuscitation, when we administer bolus high doses, we use precisely α-1 activity, which brings massive vasoconstriction everywhere, except for the coronary and cerebral blood vessels, at the same time leading to an increase in SF, BP and vascular resistance. Adrenaline is administered as a bolus dose of 0.01 mg/kg (10 μg/kg). Previously recommended subsequent 10-fold higher doses (so-called high dose epinephrine) are no longer recommended. The same dose is given intraosseously, 0.1 mg/kg is given intratracheally. Adrenaline has a number of side effects. Within the CNS it leads to anxiety, nausea. High doses can cause myocardial ischemia, arrhythmias. Although ventricular tachycardia is rare in childhood, it occurs more often with concomitant myocarditis, hypokalemia and hypoxemia. Adrenaline also has significant metabolic effects: stimulation of β-2 receptors, which are associated with Na-K-ATPase in muscles, leads to hypokalemia (infusion of 0.1 μg/kg/min. leads to a decrease in potassium by 0.8 mmol/l ). β-adrenergic mediated suppression of insulin results in hyperglycemia. Adrenaline is degraded by monoamine oxidase or catechol-o-methyltransferase. The recommended dosage is 0.005–2.0 μg/kg/min, as part of cardiopulmonary resuscitation we administer 10 μg/kg i.v. as a bolus. Adrenaline is stable when diluted to 5% glucose or 1/1 FR.

Indications:
 * shock in association with myocardial dysfunction, especially in patients after successful cardiopulmonary resuscitation or after a hypoxic-ischemic insult.
 * sepsis, where the condition did not improve after volume expansion, dopamine or dobutamine and high SVRI (low flow) persists.
 * conditions with hypotension, low CI and high SVRI.
 * cardiopulmonary resuscitation

Noradrenaline
Noradrenaline is a potent inotropic substance with a direct effect on β-1 and α-1 receptors. It has a powerful vasoconstrictive effect, as α-adrenergic stimulation is not opposed by the β-2 effect. Noradrenaline does not increase the heart rate, as it reflexively reduces the activity of the SA node through the vagus nerve and thus eliminates the expected β-1 chronotropic effect. Noradrenaline is also powerful inotropic effect. It mainly increases diastolic BP and diuresis. An increase in afterload tends to increase oxygen consumption in the myocardium, however noradrenaline reflexly reduces heart rate and thereby reduces myocardial oxygen consumption and improves coronary flow in diastole. It has no β-2 agonist effect. It is one of the most widely used drugs in the treatment of circulatory insufficiency in resuscitation care. It is the vasoconstrictor of first choice today. Noradrenaline improves perfusion in severely hypotensive children with low SVRI and normal or elevated CI. Typical choices are septic or anaphylactic shock. Noradrenaline, like other catecholamines, should be administered only after volume depletion has been completed, ideally in patients where both SVRI and CO/CI can be assessed. In children, noradrenaline is recommended for the high flow form of shock, which is refractory to volume expansion and dopamine. On the other hand, norepinephrine can increase blood pressure without improving organ perfusion. Typical cases are low CI, insufficient volume expansion, increase in PAWP. The use of high doses of norepinephrine, which increase pressure but do not improve organ perfusion, may contribute to the development of MODS. In general, however, the limitation of upper doses of noradrenaline/adrenaline is the occurrence of adverse effects, i.e. myocardial ischemia, tachycardia and arrhythmias. In case of extravasation, we quickly infiltrate the affected tissue with phentolamine (5 to 10 mg in 10 ml 1/1 FR). The recommended dosage is 0.01 to 1.0 μg/kg/min. The wide range of recommendations is due to the need for titration of continuous noradrenaline administration. Noradrenaline is stable when diluted to 5% glucose.

Indications:
 * the most frequently used drug in the treatment of circulatory insufficiency in resuscitation care, it is today the vasoconstrictor of first choice
 * severe hypotension with low SVRI and normal or elevated CI (septic or anaphylactic shock)
 * high flow form of shock that is refractory to volume expansion and dopamine.

Dopamine
Dopamine is a central neurotransmitter, it is also found in sympathetic nerve endings and in the adrenal medulla, where it is a rapidly usable precursor for the formation of noradrenaline. Dopamine affects D1 and D2 receptors (dopa receptors), which are located in the brain and vascular bed kidney, splanchnic and newborns and infants show lower sensitivity to dopamine is a tradition, but not definitively confirmed. Dopamine is recommended as the drug of first choice in children in septic shock where volume expansion has failed, dopamine is suitable in children with mild myocardial dysfunction and hypotension after cardiopulmonary resuscitation. Severe contractility or vasomotor impairment requires the use of other catecholamines. Children with primary myocardial dysfunction and in the absence of hypotension benefit more from administration of dobutamine or milrinone. At a dose below 5 μg/kg/min, the effects are dominated by influencing D-1 receptors, at a dose of 5 to 10 μg/kg/min, β-1 shows adrenergic effects, at doses of 10 to 15 μg/kg/min, it has a mixed α + β effect . Dose increase to > 15 μg/kg/min. leads to increased stimulation of α-1 receptors, increasing dose > 22–25 μg/kg/min. is no longer relevant and it is necessary to choose another inotropic agent. In shock state with hypotension, we start administration at a rate of 5 to 10 μg/kg/min., increasing the infusion rate in steps of 2 to 5 μg/kg/min. We assess the effect of the treatment according to the difference in central and skin temperature, capillary return, diuresis. When doses > 25 μg/kg/min are required, SVRI (predominance of α-receptor stimulation) increases more significantly than cardiac output. We refer to this condition as dopamine-resistant. The next step is the use of noradrenaline for high flow form (warm shock) or adrenaline for low flow (cold shock). Disadvantages of dopamine include its proarrhythmogenic effect, tachycardia and increased myocardial oxygen consumption, hypertension. With the exception of bipyridines, all inotropic agents increase myocardial oxygen consumption because they increase myocardial workload. The effectiveness of dopamine is significantly limited in patients with a depleted supply of endogenous catecholamines. Dopamine and other β-agonists decrease PaO2 by interfering with alveolar pulmonary vasoconstriction (exacerbating the V/Q imbalance). In case of extravasation, we quickly infiltrate the affected tissue with phentolamine (5 to 10 mg in 10 ml 1/1 FR). The recommended dosage is 5 to 20 μg/kg/min. Dopamine is stable when diluted to 5% glucose or 1/1 FR.

β-agonists have a hypokalemic effect (by affecting Na-K-ATPase) and reduce PaO2 (the vasodilatation induced by them in the pulmonary basin interferes with the mechanism of hypoxic alveolar vasoconstriction => deepening of the V/Q disparity when the P-L shunt increases).

Indications:
 * drug of first choice in children in septic shock where volume expansion has failed
 * suitable for children with mild myocardial dysfunction and hypotension after cardiopulmonary resuscitation

Dobutamine
Dobutamine is a synthetic analogue of dopamine. It has no dopaminergic activity. It is a potent inodilator with inotropic β-1 and vasodilatory + chronotropic β-2 activity affecting arteriolar and venous channels. Its great advantage is that it does not have its own proarrhythmogenic effect and practically does not have its own toxic effect. In septic shock, we administer dobutamine if myocardialial dysfunction prevails. However, usually the main concern is the regulation of vascular tone, and SVRI-increasing drugs are preferred. In myocardial dysfunction, dobutamine alone or in combination with dopamine increases CO and subsequently blood pressure. However, dobutamine is most often combined with noradrenaline in conditions with myocardial dysfunction associated with a high flow form of shock (sepsis) or ARDS. Dobutamine and noradrenaline are currently the most frequently used combination of vasoactive substances in resuscitation care. In children with myocardial dysfunction, dobutamine increases systolic volume and CO, without a significant increase in heart rate. Dobutamine leads to a decrease in SVR and PVR. These mechanisms explain the increase in pulse pressure.

Indications for the administration of dobutamine in pediatrics are conditions of congestive heart failure with low CI and normal or slightly reduced blood pressure (viral myocarditis, drug-induced cardiomyopathies, myocardial infarctions] ] –[[m. Kawasaki, abnormal distance of the left coronary artery)

In myocardial failure, we start with dobutamine and ensure adequate intravascular volume according to CVP. Simple volume expansion is not appropriate here. Dobutamine is the inodilator of choice today. Dobutamine can also be administered as a single catecholamine into a peripheral vein.

Adverse effects include marked tachycardia, which may increase oxygen consumption and require dose reduction or change to another agent. Rarely, it may cause atrial or ventricular dysrhythmias, especially in patients with myocarditis, electrolyte imbalance, or at high doses. Dobutamine, like other inotropic agents, must be administered with caution in patients with left ventricular outflow obstruction (hypertrophic aortic stenosis).

The recommended dosage is 2-20 μg/kg/min. Children < 1 year may be less responsive to dobutamine or delta doses of dopamine. If doses > 22 μg/kg/min. do not lead to an improvement in the hemodynamic state, we are considering changing to adrenaline. Dobutamine is stable when diluted to 5% glucose or 1/1 FR.

Indications:
 * septic shock if myocardial dysfunction predominates
 * in combination with noradrenaline in conditions with myocardial dysfunction in connection with high flow form of shock (sepsis) or ARDS
 * conditions of congestive heart failure with low CI and normal or slightly reduced blood pressure (viral myocarditis, drug-induced cardiomyopathy, myocardial infarctions - Kawasaki muscle, abnormal distance of the left coronary artery)
 * in case of myocardial failure, we start with dobutamine and ensure adequate intravascular volume according to CVP values


 * Dopamine and dobutamine are drugs that increase systolic volume.

Phosphodiesterase III blockers
Phosphodiesterase III blockers (PDE III) are divided into bipyridine (amrinone and milrinone) and imidazole (enoximone and pyroximone) preparations. They do not belong to catecholamines, their effect is through selective inhibition of phosphodiesterase III, they do not act on adrenergic receptors or lead to inhibition of Na-K-ATPase. Their effect is similar to dobutamine, i.e. especially the β-2 effect. They increase myocardial contractility, have a vasodilating effect, and improve diastolic function (lusitropic effect). The disadvantage is a whole range of side effects, led by a high proarrhythmogenic effect, the result of which can be systemic hypotension with ventricular tachycardia.

When using phosphodiesterase III blockers, most experts recommend continuous infusion to achieve steady state. Because these drugs have a long half-life, their infusion should be stopped at the first signs of tachyarrhythmia, hypotension, or an excessive decrease in SVR, especially if liver or kidney dysfunction occurs at the same time. The hypotensive effects of phosphodiesterase III blockers can be eliminated by replacing co-administered adrenaline with noradrenaline. Milrinone, as a newer agent, has fewer side effects than amrinone, and is a more selective PDE III inhibitor.

Indications for amrinone/milrinone in children are:
 * normotensive patients with low CI but high SVRI despite epinephrine or nitrate infusion
 * low cardiac output in dilated forms of cardiomyopathy when other inotropic support fails
 * patients with down-regulation of β-1 and β-2 receptors
 * with toxic effects of nitrates
 * conditions with severe heart insufficiency refractory to other treatment
 * postoperative conditions in cardiac surgery

Drug affecting venous return (preload)
Administering preload = diuretics and venodilators in heart failure with reduced contractility will improve cardiac performance by reducing ventricular size and reducing wall tension. First of all, we reduce preload by restricting fluids and administering diuretics.

Diuretics
Diuretics relieve symptoms of pulmonary congestion and peripheral edema. We most often usefurosemide in a dose of 0.5–2 mg/kg i.v. as a bolus according to diuresis, or continuously up to a maximum total dose of 10 mg/kg/day. By directly acting on the loop of Henle, it causes the excretion of ions Na, K, Cl and body water. It has a quick and short-term effect.

During long-term diuretic treatment, when there is a risk of developing secondary hyperaldosteronism and hypokalemia, spironolactone is indicated in a dose of 1-3 mg/kg/day divided into 3 doses. Spironolactone is a competitive aldosterone inhibitor acting on the distal renal tubule. It has a very weak diuretic effect by itself, but potentiates the effect of other diuretics. It partially antagonizes the loss of K ions. In combination with ACE inhibitors or excessive potassium substitution, it causes hyperkalemia.

A farm affecting preload and afterload
The common denominator for this group of drugs is reduction of peripheral vascular resistance. They have a combined effect on veins and arteries. It should be emphasized that high peripheral vascular resistance is a frequent symptom during shock states in children. We are talking about the fact that hypodynamic shock is typical for children. Affecting the resistance and capacity of the systemic vascular bed has an effect on cardiac performance. An increase in peripheral vascular resistance with unchanged preload and contractility decreases cardiac output. The use of vasodilators and other drugs with a relaxing effect on the smooth muscle of peripheral vessels can modify cardiac performance in heart failure. Peripheral vascular vasodilatation reduces myocardial afterload. By increasing the capacity of the systemic flow, the preload of the myocardium also decreases and the filling volume of the heart decreases. However, the reduction of peripheral resistance carries the risk of systemic vasodilation, which in the case of subclinical or unrecognized hypovolemia can lead to life-threatening hypotension. Simultaneously with the reduction of SVR, the regulatory mechanisms of fluid redistribution are disrupted. When using vasodilator therapy, it is advisable to monitor filling and systemic pressures. Medicines that reduce high SVR include sodium nitroprusside, nitroglycerin and ACE inhibitors, and to a lesser extent dehydrobenzperidol or chlorpromazine.

Sodium nitroprusside
Nitroprusside is a fast-acting peripheral vasodilator. It has a direct vasodilating effect on arterioles and veins. It primarily reduces afterload and thus increases cardiac output. The result is reduced filling of the left ventricle, reduction of pulmonary congestion, reduction of volume and pressure in the left ventricle, better emptying of the left ventricle in systole, reduced oxygen consumption by the myocardium. Its effect is tied to its immediate administration, i.e. after stopping the infusion, the effect is immediately lost. When using it, invasive blood pressure monitoring is absolutely necessary. Prolonged administration may lead to a rise in serum cyanide levels; their control is necessary. During intoxication, disorders of consciousness, MAC appear. The recommended dose is 0.5–10 μg/kg/min, the dose is titrated according to the effect. As a rule, we start with a low dose and, depending on the effect, increase the dose by approx. 0.5 μg/kg/min after 10 minutes. Nitroprusside can be combined with dopamine or dobutamine because they have a synergistic effect on increasing cardiac output. Due to its drastic effect, which can also be associated with serious complications, we only use nitroprusside in the most severe cases.

Nitroglycerin
Venodilators are indicated for elevated end-diastolic pressure. The main representative is nitroglycerin. It has a direct venodilating effect, it dilates the smooth muscle of the vascular wall, predominantly systemic veins and coronary arteries. It reduces venous return and reduces congestion in the systemic and pulmonary basins. In low doses, it leads to venodilatation and reduction of preload. High doses cause more pronounced vasodilation in the pulmonary basin (cave: congestion!), dilation of arterioles and reduction of afterload. Pharmacological effects depend mainly on the state of the intravascular volume, less on the dose (hypovolemia increases the risk of hypotension). Usual doses are 0.25–5 μg/kg/min continuously i.v.

ACE inhibitors
ACE inhibitors lead to vasodilation and reduction of aldosterone secretion. The result is increased excretion of sodium, which leads to a decrease in systemic peripheral resistance, a decrease in EDP and an increase in cardiac output. Another positive effect is the ability to remodel the hypertrophic myocardium of the ventricles. A representative is e.g. enalapril, doses p.o. 0.15–0.5 mg/kg/d in 1–2 doses, for i.v. treatment 5–10 μg/kg/dose 1–3 times within 24 hours

Steroids
Administration of hydrocortisone should be reserved for conditions unresponsive to adequate treatment with volume expansion and inotropes or situations with suspected or proven adrenal insufficiency. Children with septic shock and purpura, with previous chronic corticoid therapy and with adrenal or pituitary abnormalities are a risk group. The exact definition of adrenal insufficiency is not formulated, in case of septic shock resistant to catecholamines, the finding of a cortisol level < 500 nmol/l is considered to be its sign. The optimal dosage of steroids in children is not formulated, the most often recommended doses vary from 1 to 2 mg/kg of hydrocortisone as stress doses, alternatively 200 mg/d divided into 3-4 doses regardless of body weight. One of the recent recommendations for the administration of hydrocortisone: 0.18 mg/kg/hour. continuously. Recent meta-analyses have confirmed that methylprednisolone-type steroids in high doses, i.e. 30 mg/kg, are ineffective or even harmful in shock states.

Metabolic support
In cardiogenic shock, we administer fluids at a dose of 80-100% of the normal daily requirement, more precisely according to CVP and PAWP values. For other types of shock, we initially increase the daily fluid requirement to 150-200% of normal, and a significantly positive water balance is not unusual during the first day of therapy. bicarbonate therapy is chosen in a situation of severe MAC (pH < 7.1, HCO3 < 8) despite adequate volume expansion.

Other therapies
The finding of hypocalcemia can lead to a picture of left ventricular dysfunction, which is completely reversible after calcium correction. Especially in the smallest children, where glycogen reserves are reduced, we can find hypoglycemia. In general, the last option, the so-called rescue therapy, is ECMO (extracorporeal membrane oxygenation).

Complications of shock states
As part of the shock, we can find various multisystem dysfunctions. Their diagnosis is as important as their treatment. Possible complications of any shock state are:
 * acute tubular necrosis
 * ischemia of intestine: NEC, perforation
 * myocardial ischemia
 * CNS damage: intracranial hypertension, convulsions
 * pancreatitis
 * DIC
 * rhabdomyolysis
 * metabolic disorders
 * MODS

Source

 * HAVRÁNEK, Jiří: Šok. (edited)

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