Anesthesia and Septic Shock: Pharmacological Approaches and Applications

2.1 Volatile anesthetics

Volatile anesthetics should be used with caution in patients with septic shock, as the vasodilating effects of these agents may further decrease blood pressure in septic patients. When using volatile anesthetics such as isoflurane and sevoflurane, dose adjustments are necessary to maintain hemodynamic stability. Isoflurane may preserve cardiac function by reducing myocardial depression, while its general vasodilatory effects may lower blood pressure. Careful hemodynamic monitoring is required when using these agents in septic shock [6].

Volatile anesthetics also have anti-inflammatory effects. Agents such as isoflurane and sevoflurane may reduce the inflammatory response during sepsis by suppressing the production of inflammatory cytokines. These effects of volatile anesthetics on the immune system in sepsis patients may be important for treatment strategies, but careful monitoring is required in clinical practice [5].

2.2 Intravenous anesthetics

Propofol: Propofol should be used with caution in patients with septic shock. The vasodilating and myocardial depressant effects of propofol may exacerbate hypotension in septic patients. When using propofol, especially in patients with septic shock, the lowest effective dose should be preferred, and the patient’s hemodynamic status should be carefully monitored. Propofol may increase the inflammatory cytokine response, a factor to be considered in septic patients [6, 7].

Ketamine: Ketamine is an agent that increases cardiovascular support and can be safely used in septic shock patients. The sympathomimetic effects of ketamine can increase blood pressure and stabilize myocardial depression during septic shock. In addition, ketamine has anti-inflammatory effects; it can reduce the inflammatory response by suppressing cytokine production. These properties make ketamine an important option for achieving hemodynamic stability and controlling inflammation in patients with septic shock [8, 9].

Etomidate: Etomidate may be preferred in septic patients because it is a more hemodynamically stable agent. However, etomidate has adrenal suppressive effects, which may be detrimental to septic patients in long-term use. Although a single dose of etomidate is considered safe in septic shock patients, the dose should be carefully adjusted to minimize the effects of adrenal suppression (Table 1) [7, 9].

2.3 Role of opioids

Opioids play an important role in the management of analgesia in patients with septic shock. Short-acting opioids (fentanyl, alfentanil, and remifentanil) can be used safely in patients with septic shock and are preferred because they have less effect on blood pressure. These agents can help maintain hemodynamic stability. However, the immunosuppressive effects of opioids should be considered. High doses of opioids may suppress the infection response in septic patients and this should be carefully monitored [7, 8].

3.1 Vasopressor and inotropic support

In patients with septic shock, vasopressors and inotropes are often used to maintain hemodynamic stability. The most commonly used vasopressors are norepinephrine and epinephrine. Norepinephrine is the first-line vasopressor for septic shock and increases systemic vascular resistance and blood pressure by peripheral vasoconstriction [10]. Adrenaline may be preferred, especially in refractory septic shock, because of both its vasopressor and inotropic effects. Adrenaline is characterized by its effects of increasing cardiac output and increasing systemic vascular resistance (Figure 1) [11].

Dobutamine is used to increase cardiac contractility in septic patients with low cardiac output. Especially when combined with norepinephrine, this agent can improve organ perfusion by increasing hemodynamic support [10]. Vasopressin is rarely used as third-line therapy and is preferred in cases of septic shock refractory to vasopressors. Vasopressin is often given in low doses (0.01–0.04 units/min) in addition to norepinephrine, and this combination provides better blood pressure control [11].

3.2 Fluid resuscitation

Fluid resuscitation in septic shock is the first step in achieving hemodynamic stability. The goal is to improve cardiac output and tissue oxygenation by increasing effective intravascular volume. Crystalloids (e.g., isotonic saline) are usually the first choice of fluid because large studies have shown a favorable effect of crystalloids on mortality [6]. Colloids, on the other hand, can be used especially in patients with hypoalbuminemia, but their cost is higher and some studies have reported adverse effects on renal function [9].

Another important issue to consider in fluid therapy is the appropriate titration of fluid volume. Fluid overload can lead to pulmonary edema and other complications. Therefore, patients’ hemodynamic responses should be closely monitored, and fluid therapy should be adjusted according to clinical needs [11.pdf]. Optimal fluid management is a balanced approach in which crystalloids are the first choice to ensure adequate organ perfusion, but colloids can also be used when necessary [9].

4.1 Preoperative evaluation

Preoperative evaluation of patients with septic shock is one of the most critical steps in anesthesia management. The presence of organ dysfunction in these patients and the effects of sepsis on the cardiovascular, renal, and respiratory systems are critical to the surgical and anesthetic process. Careful assessment of the hemodynamic status provides information about the patient’s fluid balance, blood pressure, and perfusion status. Adequate fluid resuscitation and vasopressor support should be provided. As septic shock leads to hypotension and hypoperfusion, patients should be brought to preoperative cardiovascular stability [11].

Respiratory status is a critical parameter in septic shock. Complications such as acute respiratory distress syndrome (ARDS) may occur in these patients, and respiratory support should be planned. Renal function is often compromised in sepsis and acute kidney injury is common. Preoperative assessment of renal function, diuresis monitoring, and renal replacement therapy, if indicated, play an important role in the planning of anesthetic management [10].

4.2 Anesthesia planning

Anesthetic planning should focus on achieving and maintaining hemodynamic stability in patients with septic shock. These patients are usually hemodynamically unstable, and drug selection should be based on the effects of anesthetic agents on the cardiovascular system. Ketamine is the agent of choice in patients with septic shock because of its effects on cardiovascular support. Etomidate provides hemodynamic stability despite the risk of adrenal suppression when used in a single dose and is considered safe in septic patients [9].

Agents such as propofol should be used with caution in septic shock patients due to its cardiovascular depressant effects. Propofol may worsen hypotension, so careful dose adjustment and continuous hemodynamic monitoring should be used. Vasopressors and inotropic agents are commonly used during anesthesia in patients with septic shock and may be given as continuous infusions to support blood pressure. Norepinephrine is the preferred first-line vasopressor in septic shock and plays an important role in blood pressure stabilization [6].

Invasive hemodynamic monitoring is of great importance in the perioperative period. Continuous blood pressure monitoring by arterial catheterization, fluid balance monitoring by central venous catheterization, and more detailed hemodynamic monitoring by pulmonary artery catheterization should be performed as needed. Echocardiography is also an important tool that can be used to assess cardiac function, especially in patients with septic shock [11].

4.3 Postoperative care

Postoperative care of patients with septic shock requires a multidisciplinary approach in the ICU. In the postoperative period, maintenance of hemodynamic stability, infection control, and monitoring of organ function are critical. Most patients require continuous monitoring in the ICU due to sepsis-related organ dysfunction. Optimal management of therapies such as fluid balance, maintenance of vasopressor and inotrope support, and ventilatory support is essential [9].

In the postoperative period, it is necessary to monitor renal function and assess the need for dialysis, as acute kidney injury due to sepsis may adversely affect the recovery process. Neurological monitoring is also important, and particular attention should be paid to neurological complications that may develop after prolonged hypotension and hypoperfusion [11.pdf]. In addition, long-term effects of anesthesia in septic patients may include cognitive dysfunction and post-sepsis syndrome; therefore, early mobilization and rehabilitation planning is an integral part of postoperative care [11].

5.1 Organ dysfunction and supportive therapy

Postoperative multiple organ dysfunction (MODS) is a common and serious complication in patients with septic shock. Acute renal failure and respiratory failure are more common due to the inflammatory response that develops during sepsis. Monitoring of renal function and initiation of renal replacement therapy when necessary plays an important role in postoperative management [5.pdf]. Pulmonary complications may require ventilatory support in patients with sepsis, and lung protective strategies (such as low tidal volume ventilation) should be used [7].

5.2 Septic encephalopathy and neurologic monitoring

Septic encephalopathy is a common neurologic complication in patients with septic shock and requires careful neurologic monitoring in the postoperative period. Hypoperfusion and inflammation during sepsis can lead to impaired brain function. Cognitive impairment and delirium are common long-term sequelae in these patients [8]. Neurological monitoring and cognitive rehabilitation strategies play a critical role in the management of these complications [6].

5.3 Post-sepsis syndrome and rehabilitation

Post sepsis syndrome can have long-term physical, cognitive, and psychological effects in patients with septic shock. This syndrome is more common in elderly patients. Early mobilization of patients in the postoperative period and physical therapy can reduce the effects of post-sepsis syndrome [9.pdf]. In addition, cognitive rehabilitation may be beneficial in reducing the neurological effects of septic shock [10].

5.4 Nutritional support and metabolic management

Nutritional management is critical to support the postoperative recovery of patients with sepsis. Optimal enteral and parenteral nutrition strategies should be implemented in these hypercatabolic patients. Nutritional support is essential to support the immune system and accelerate the healing process [5].

5.5 Long-term cardiac follow-up

The cardiac function of septic shock patients should be monitored for a long time in the postoperative period. Regular assessment of cardiac output and ventricular function by non-invasive methods such as echocardiography is recommended [7]. Cardiac rehabilitation programs should also be planned to minimize the long-term effects of cardiovascular dysfunction in septic shock [11].

6.1 Sepsis and suppression of immune response

Septic shock leads to an excessive inflammatory response in the body, resulting in significant suppression of the immune system. This leads to impaired immune cell function and an imbalance in cytokine production in patients. In particular, the excessive release of pro-inflammatory cytokines triggers an anti-inflammatory response that suppresses the immune system, leaving patients vulnerable to infection [5]. Immunosuppression after sepsis can lead to an easier spread of infections and therefore regulation of the immune response in patients with sepsis is of vital importance.

6.2 Immune modulatory therapies

Immunomodulatory strategies are treatments used to regulate the immune system in patients with septic shock. These strategies aim to suppress the cytokine response in combination with drugs that regulate the immune response, such as glucocorticoids. However, the effect of these therapies on survival after sepsis is controversial. In some studies, short-term use of glucocorticoids has been shown to accelerate the recovery process in septic shock patients, but these agents may further suppress the immune system when used long-term [7].

IVIG (intravenous immunoglobulin) is another immunomodulatory strategy used to support the immune system during sepsis. By increasing antibody levels, IVIG can strengthen the body’s defenses against infection and stabilize the inflammatory response [12]. In patients with septic shock, this treatment may be effective in restoring immune function.

6.3 Infection control

Control of infections in patients with septic shock should be a multidisciplinary approach in the intensive care unit. Antibiotic treatment should be initiated early to rapidly control infections. Empiric antibiotic therapy should be performed with broad-spectrum antibiotics in particular and should be limited according to culture results [11].

However, implementation of aseptic techniques and strict infection control measures in the ICU is critical to minimize the risk of recurrent infection. It should be noted that catheters and invasive monitoring devices can be a source of infection and regular replacement of these devices should be ensured [13].

6.4 Immune system restoration and rehabilitation

In patients recovering from septic shock, it may take time for the immune system to fully recover. Restoring immune system function in these patients requires a multidisciplinary approach, including nutritional supplementation, physical rehabilitation, and mental health support. Micronutrient supplements should be administered, especially in cases of deficiency of immune-supporting elements such as zinc, selenium, and vitamin C [8.pdf]. In addition, these patients should undergo long-term immune monitoring and be closely monitored for recurrent infections.

7.1 Sepsis and suppression of immune response

Septic shock is a highly complex clinical condition that requires a multifaceted approach to anesthesia management. Hemodynamic instability, organ dysfunction, and infection control are the major challenges that anesthesiologists must continually address. Fluid management, use of vasopressors and inotropes, careful selection of anesthetic agents, and perioperative hemodynamic stability are the cornerstones of anesthesia management in patients with septic shock [5].

Maintaining hemodynamic stability in these patients is one of the major challenges in anesthesia management. Stabilization of blood pressure and organ perfusion with vasopressor and inotropic agents is critical for successful surgical intervention and recovery [7]. At the same time, complications such as acute renal failure require continuous monitoring of patients’ fluid balance and renal function [9].

Immune modulation and infection control are other challenges in septic shock patients both pre- and postoperatively. The use of aseptic techniques to minimize the risk of infection, broad-spectrum antibiotic therapy, and stabilization of the immune response are important components of anesthesia and intensive care management [8].

7.2 The future of pharmacological approaches

The future of anesthetic management of septic shock is aimed at optimizing existing pharmacological approaches and developing new therapeutic strategies. The effects of agents such as volatile anesthetics, both in providing hemodynamic stability and suppressing the inflammatory response, may lead to larger studies in the management of septic shock. Research into the anti-inflammatory effects of these agents may lead to better control of the immune response in sepsis.

In terms of intravenous anesthetics, drugs such as ketamine will remain an important treatment option in septic shock due to their potential to provide hemodynamic stability and reduce the inflammatory response. Similarly, the development of new dosing protocols to reduce the risk of adrenal suppression with etomidate and a better understanding of the long-term use of this agent is being sought [7].

Recent research on vasopressors and inotropic agents includes advances toward safer and more effective ways to provide hemodynamic support in patients with septic shock. In particular, combinations of norepinephrine and vasopressin have been shown to provide better outcomes in septic shock patients, and further studies are needed to determine the optimal use of these agents [10].

7.3 New treatment modalities and research

In the future, more targeted therapeutic strategies are expected to be developed for the treatment of septic shock. Immune modulation strategies are among the leading treatment modalities targeting the immune system in septic shock patients. In particular, studies on the effects of IVIG and glucocorticoids on sepsis and septic shock are investigating safer and more effective use of these agents [14].

In addition, new therapeutic modalities are being developed to accelerate the repair and recovery of organs damaged during sepsis using cellular therapies and biological agents. Research in this area may lead to more specific and personalized treatment protocols by targeting the mechanisms of sepsis that cause organ failure [15].