Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Let's get started with our team timeout. Our patient today is the sepsis and critically ill or compromised patient module from the general surgical curriculum and the operation or topic we'll be covering today is essentially an introduction to sepsis and critically ill patients. We're going to be going over some of the pathogenesis and consequences of SIRS, MODS, ARDS.
shock and also talk a little bit about some of the medications used in the intensive care setting. So let's start off by talking about systemic inflammatory response syndrome or SIRS. SIRS is defined as a dysregulated host inflammatory response. to an injury or infection. The reason it says injury or infection is because
Obviously, SERS can happen in infection, but it can also happen in other states, such as trauma and pancreatitis, for example, which are not infectious processes. The diagnosis is... defined by two or more of the following criteria, which I like to remember as heart, H-A-R-T. So H is for heart rate more than 90. A is for abnormal white cell count. more than 12 or less than 4. R is for respiratory rate, more than 20. And T is for temperature, more than 38 or less than 36.
We're expected to know the pathophysiology of SIRS. And the way I remember this is by thinking of it as an imbalance between the pro-inflammatory and the anti-inflammatory cascades. It can be thought of in three different stages. So stage one is the actual inner salt itself. And so this is either an infection or activation of an inflammatory process such as tissue damage and trauma or...
activation of trypsin in pancreatitis. This insult leads to cytokine production, and the important cytokines to remember are TNF-alpha, interferon gamma, and interleukin 1, 6, and 8. And these lead to commencement and activation of the inflammatory cascade. These cytokines are released from the tissue macrophages, monocytes, mast cells and platelets. The second stage is the spillover of these inflammatory cytokines into the systemic circulation, which then recruits
more cells to help with the local response. So this includes recruitment of polymorphonuclear lymphocytes, more macrophages and platelets. The interleukin-1 and TNF-alpha cause a fever. The cytokines... activate the release of stress hormones like noradrenaline and vasopressin, and there's activation of the renin-angiotensin system. They also result in the activation of the coagulation and the complement cascades.
Components of the complement cascade such as complement 3A and 5A are potent vasodilators which cause systemic vasodilation and hypotension. Other substances including prostaglandins and leukotrienes are released, which cause endothelial damage and increase the vascular permeability of vessels.
This leads to further fluid loss, hypotension and contributes to multi-organ dysfunction, especially in the lung and the kidneys. So the third stage of SIRS is usually a compensatory anti-inflammatory response, which is often written as CARS or CARS. The compensatory anti-inflammatory response is supposed to stop this inflammatory reaction, and it's usually mediated by interleukin 4 and 10, which...
inhibit the production of further inflammatory cytokines. If there is an imbalance in this inflammatory response and compensatory anti-inflammatory response, then that's when patients are subjected to the full gamut or spectrum of the inflammatory response. So the next pathology I want to talk about is sepsis. Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.
The diagnosis is as per the sepsis 3 definition, which states that sepsis is diagnosed in the setting of confirmed or suspected infection. plus an increase in two points in the SOFA score. SOFA stands for Sequential Organ Failure Assessment. And this is a score that basically looks at different organ systems. So the respiratory system, coagulation, liver, cardiovascular. CNS and renal systems and gives a score of zero to four in each of these with an increasing number for dysfunction.
Or an alternative and the one I think I'll remember for the exam is instead of looking at an increase in two SOFA points, is looking at the Q SOFA score. So the QSOFA score looks at only three criteria. And I remember these by the mnemonic HAT, H-A-T. So H is for hypotension with a systolic blood pressure less than 100. A is for altered mental status, so GCS less than 15. And T is for tachypnea, so a respiratory rate of more than 22.
And if you score two or more of these factors and you have a confirmed or suspected infection, then this is diagnosed as sepsis. A further subset of sepsis is septic shock, which is where there's underlying cellular or metabolic abnormalities that are profound enough to increase mortality. And the diagnosis of septic shock is the presence of sepsis, which we just talked about, plus despite adequate volume resuscitation, both of the following.
So persistent hypotension requiring a vasopressor to maintain a MAP greater than or equal to 65 and a lactate greater than or equal to 2. So the pathophysiology of sepsis and septic shock is pretty much the same as the SERS pathophysiology, except that in these cases, it's a septic or infectious insult that's causing this. And so the initial infection is recognized as non-self with the pathogen-associated molecular patterns or PAMPs.
Bacteria themselves can release toxins that cause direct tissue damage, which then causes the release of cytokines, which if you remember was TNF-alpha, interferon gamma, interleukin 1, 6, and 8. And then these spill over into the systemic circulation and activate more cells to come and help with the fight against the pathogen. And this activates other cascades such as the complement cascade with C3A and 5A being vasodilators, release of prostaglandins and leukotrienes.
causing increased vascular permeability and also direct damage to vessels, causing increased vascular permeability, as well as a prothrombotic state, which can cause microthrombosis and disseminated intravascular coagulation. Other systemic effects include a fever because of interleukin-1, increased white cell count due to bone marrow response and the production of new white cells.
release of acute phase reactants such as CRP, fibrinogen, and serum amyloid A, and also metabolic responses including hyperglycemia and insulin resistance. The next topic I want to talk about is multi-organ dysfunction syndrome or MODS. The definition of MUDs is a hypometabolic immunodepressed state with clinical and biochemical evidence of decreased function of the body's organ systems.
And multi-organ dysfunction syndrome is often seen as a consequence of another acute illness or injury. The diagnosis of MODS is made where there's presence of SIRS. and dysfunction of at least two organ systems. The pathogenesis is not entirely clear, but it's thought to be a continuation of the systemic inflammatory response syndrome, which we've already talked about.
And it's thought that the contributing factors include a number of different things. So this includes complications or reduction in the macro circulation of the body. And this could be due... to systemic vasodilation because of leukotrienes and prostaglandins, as I've already talked about. It could be due to fluid losses into third spaces due to increased vascular permeability. and this causes hypotension and reduced oxygen delivery to tissues.
There's microcirculatory changes in SIRS. And so activation of the coagulation cascade causes microvascular thrombi. The low flow state results in increased blood. And there's also endothelial damage because of the inflammatory response that may impair blood flow to organs. The inflammation itself and the... pro-inflammatory factors and circulating cytokines can cause direct damage to tissues. There's translocation of microorganisms from the gastrointestinal tract.
And patients are also in a immunosuppressed state because the compensatory anti-inflammatory response is trying to stabilize the SERS response. And this actually means that people are less able to fight off. infections. It's likely that all of these factors work in concert and obviously how much each of them contribute to organ dysfunction is going to depend on the initial insult, stage of the illness, the underlying organ reserve.
of the patient and the therapies and treatments that are given to the patient. Some of the organs that are affected commonly in multi-organ dysfunction syndrome include the renal system. So patients often have an acute kidney injury and may be acidotic and oliguric. And this is thought to be because of hypovolemia and also circulating nephrotoxic compounds. And patients may need filtration while their renal function is recovering.
Patients may develop lung injury, such as acute respiratory distress syndrome, which we'll talk about in a minute. Cardiomyopathy or poor cardiac function can be because of a number of factors. The hypotension itself will reduce the blood flow to the coronary vessels and cause myocardial ischemia. There's loss of afterload due to the systemic vasodilation.
There's loss of the circulating volume and the cardiac return because of the hypotension and hypovolemia because of third spacing. And there's also myocardial depression because of acidosis and electrolytes. abnormalities patients may have a decreased GCS because of hypotension and some of the side effects or compounds from the infectious and inflammatory response
Patients will have gastrointestinal dysfunction with increased GIT permeability and bacterial translocation. They may develop an ileus. They may develop stress ulcers. acalculus cholecystitis, or even gastrointestinal ischemia due to the low flow state. They can have ischemic hepatitis. coagulopathy with a disseminated intravascular coagulation, and also immunosuppression and bone marrow suppression with pancytopenias developing.
And management of multi-organ dysfunction syndrome is essentially supportive and trying to identify the underlying cause and treat that and obviously address any complications as they arise. Gosh, we're slowly making our way through this list of critically ill patient issues. The next one to talk about is shock. So shock is a state of organ hypoperfusion. with resultant cellular hypoxia, cellular death, and dysfunction of the organ. There's multiple different mechanisms or categories of shock.
This includes hypovolemic shock, cardiogenic shock, a distributive shock, and obstructive shock. So I'll talk a little bit about each of these different groups. So hypovolemic shock is a type of shock where there's inadequate organ perfusion due to a loss of intravascular volume. And this results in a drop in the cardiac.
preload and reduction in the macro and micro circulation to organs. And the two main types of hypovolemic shock are hemorrhagic, which we commonly deal with as surgeons in trauma. and non-hemorrhagic shock, which could be due to gastrointestinal losses, renal losses. We see this in burns. and in third spacing and conditions such as pancreatitis and small bowel obstruction.
Cardiogenic shock is a primary disorder of cardiac function, which reduces the heart's capacity to pump and can cause systolic or diastolic cardiogenic shock. This leads to a decrease in the cardiac output and therefore perfusion of organs and causes can include cardiomyopathy, arrhythmia or valvular issues. The next type is distributive shock, which is usually characterized by peripheral vasodilation, which as I've already mentioned today, can be due to infection and SIRS.
And so this is a state of relative hypovolemia due to the redistribution of the intravascular volume. And it's the most frequent form of shock. The different types include septic shock. shock due to SERS, anaphylactic shock where there's a release of histamine from mast cells or basophils, and neurogenic shock.
where there's an imbalance between the sympathetic and parasympathetic regulation of the heart and vascular smooth muscle that leads to profound vasodilatation. And then the last one was obstructive shock. And this is where there's decreased left ventricular function due to an extra cardiac cause. And this includes a large pulmonary embolism and severe pulmonary hypertension or pericardial tamponade.
and pneumothorax. So the diagnosis of shock is defined as The presence of both hypotension with a systolic blood pressure less than 90 or a MAP of less than 65 requiring vasopressors. as well as markers of tissue hypoperfusion. So this includes a blood lactate more than two or a base deficit. The pathophysiology of shock is that there is hypoxia at a cellular level, which leads to cellular and biochemical changes.
that lead to acidosis and decreased regional blood flow, which then worsens the tissue hypoxia. And there are three main phases of shock. So the first shock is the compensated phase. And this is where compensatory mechanisms will counter the decreased tissue perfusion. And so these are things such as a reflex tachycardia and peripheral vaso. constriction to shunt blood back to the essential organs.
The second stage of shock is where you have the classic signs and symptoms of shock. And so this is where the compensatory mechanisms have been overcome and patients are starting to have a reduction in their blood pressure, increased respiratory. rate, decreased pulse pressure, and are going to have evidence of end-organ hypoperfusion with oliguria and CNS changes.
And then the third stage is the end stage with organ dysfunction, multi-organ dysfunction, failure of organs and eventual death of the patient. So the next condition I want to talk about is adult respiratory distress syndrome, also known as ARDS. And the definition of this is a protein-rich pulmonary edema. that leads to severe hypoxemia and impaired carbon dioxide excretion. The pathogenesis of ARDS is it's an inflammatory injury to the lung endothelium and epithelium.
which leads to a marked increase in the lung vascular and epithelial permeability and the passage of protein-rich edema fluid into the air spaces. The lung injury can be caused by multiple things. Some examples include injury from neutrophil dependent and platelet dependent damage to endothelial and epithelial barriers of the lung.
and can also be found in other conditions such as SIRS from the systemic inflammation and cytokine release and in inhalation or lung injury, for example. Due to the epithelial and endothelial... injuries, there's an impaired removal of the pulmonary edema fluid, which delays resolution of this condition and deprives the lung of surfactant.
And the initial injury can be compounded by ventilator-associated lung injury. Some common conditions that ARDS is associated with include pneumonia, non-pulmonary infections and systemic sepsis, aspiration, trauma with shock and hemorrhage, pancreatitis, transfusion related. lung injuries, and drug reactions.
And the management of ARDS is to prevent secondary ventilator-associated lung injury. And so they will use lower tidal volumes and reduce airway pressures to facilitate inflammation resolution and repair. of the epithelium in the lungs. And so to finish us off today, I just wanna... do a quick run around of what some of the medications the intensive care might use for low blood pressure.
So broadly, ionotropes and vasopressors have their mechanism of action on different receptors. So this includes the beta-1, beta-2, alpha-1. and dopaminergic receptors. So beta-1 adrenergic receptor stimulation results in increased myocardial contractility. Beta 2 adrenergic receptors act on vascular smooth muscle and result in vasodilatation. Alpha 1 adrenergic receptors are on arterial...
vessels and result in smooth muscle contraction. So they cause vasoconstriction and an increase in the systemic vascular resistance. And stimulation of dopaminergic receptors, D1 and D2, in the kidney and the splanchnic vasculature results in renal and mesenteric vasodilation. So in summary, beta agonists lead to positive ionotropy and increased myocardial contractility, as well as vasodilatation. And alpha agonists lead to vasoconstriction.
So what are the pharmacological agents that might be used in ICU and really basically how do they work? So the first group are known as vasopressors and these are probably the most commonly used ones. These vasoconstrict and they sometimes also will help improve cardiac output. They increase the systemic vascular resistance due to peripheral vasoconstriction and this improves mean arterial pressures and perfusion to organs.
Examples include noradrenaline, vasopressin, phenylephrine, and dopamine at very small doses. So noradrenaline is both a vasoconstrictor and will improve cardiac output. Vasopressin is only a peripheral vasoconstrictor acting on the V receptors of smooth muscle. And phenylephrine causes peripheral constriction due to activation of the alpha adrenergic receptors.
The second broad category are ionotropes, and these increase the cardiovascular contractility. So they improve cardiac output, improve the mean arterial pressure, and therefore improve perfusion. Types include dopamine at high doses, dobutamine, and milrinone. But milrinone does improve cardiac output but causes peripheral vasodilation and pulmonary vasodilation. And a general rule is that a mean arterial pressure of 60 to 65 is required to perfuse vital organs.
And that completes this episode on an introduction to the critically ill surgical patient. we went over a number of the different conditions or diagnoses that can happen to these patients and some of the pathophysiology, which definitely comes up in the exam. I hope you found this useful. Please remember to rate, review and subscribe to the podcast. It makes it easier for others to find. And I do love reading your reviews. It's time to close up.
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