Surgical Critical Care

Pain and Agitation

Pain is a ubiquitous but often underrecognized and inadequately treated symptom for the critically ill patient. In the ICU setting, sources of pain include traumatic injuries, burns, surgical wounds, underlying illness, and/or noxious stimuli (e.g., tracheal intubation, mechanical ventilation, invasive lines, etc.). Pain is a source of fear and anxiety that, if not properly addressed, contributes to physiologic alterations that can negatively impact patient outcomes and delay recovery. Although the sensation of pain is subjective, there are several measuring tools and scales to quantify pain as an objective data point that can be treated and easily reassessed for improvement. In patients who are able to communicate, the visual analog scale and numeric rating scale are used and provide reliable means for assessment and treatment; however, noncommunicative, altered, or comatose patients must rely upon the observant and attentive physician or nurse to identify the visual cues and physiologic alterations (e.g., tachycardia, hypertension, tachypnea, diaphoresis, etc.) that coincide with uncontrolled pain. If objective data are unavailable, one is better off to presume the presence of pain and provide appropriate treatment.

Opioids have traditionally been the first-line therapy for pain as they are centrally acting, highly effective for nonneuropathic pain, have a rapid onset, and can be administered via multiple routes (enteral, intravenous [IV], transdermal, etc.). Unfortunately, opioids are often overprescribed, leading to untoward side effects, patient abuse, and addiction. Deleterious side effects including nausea, vomiting, pruritis, sedation, respiratory depression, and bowel dysfunction result in unnecessary complications, prolonged hospital length of stay, and increased morbidity. Prolonged use can also result in physiologic dependence, tolerance, and opioid-induced hyperalgesia. Enhanced recovery after surgery protocols and the practice of utilizing multimodal therapies that work synergistically to alleviate pain and provide sedation are paramount in combating the opioid epidemic that currently plagues the United States. Combining the ability to perform regional anesthetic blocks along with nonopioid adjuncts with varying mechanisms of action such as acetaminophen, nonsteroidal anti inflammatory agents, gabapentinoids, tramadol, and muscle relaxants results in more effective analgesia and lower overall opioid requirements. The use of multimodal pain medications has become the standard of care to reduce opioid reliance and should be implemented widely.

In the same manner that pain is assessed and treated, agitation is quantified using various scoring systems to include the Richmond Agitation-Sedation Scale. When a patient is agitated, it is important that a thorough assessment of any underlying treatable etiologies is completed prior to initiating a pharmacologic intervention. Clinical guidelines have been recently updated and published by the Society of Critical Care Medicine as to the management of the agitated ICU patient. The most commonly used sedatives in the ICU include propofol, benzodiazepines, and dexmedetomidine. When deciding on which agent to use, considerations must include the expected duration and depth of sedation required, comorbidities, which may affect pharmacokinetics or metabolic clearance, and potential drug interactions with other medications the patient may already be receiving.

Propofol is a highly protein-bound, lipophilic molecule that is frequently utilized in the ICU. The exact mechanism of action is not fully elucidated, but it is thought to potentiate γ-aminobutyric acid (GABA) receptors resulting in amnesia but without analgesia. Because propofol is highly lipophilic, it readily traverses the blood-brain barrier and results in rapid onset of action in less than 1 minute as well as a short duration of action as it is quickly distributed into peripheral tissues and readily metabolized by the liver. Rapid clearance of propofol makes it the ideal drug for daily sedation weans to assess a patient’s neurologic status. Hypotension and cardiovascular depression are commonly seen with propofol administration, especially in the hypovolemic patient. The most serious potential side effects of propofol infusion include pancreatitis, hypertriglyceridemia, and propofol infusion syndrome. Propofol infusion syndrome is a rare complication associated with prolonged and/or high doses of propofol administration that is thought to be caused by mitochondrial respiratory chain inhibition or impaired mitochondrial fatty-acid metabolism. Clinical features include bradycardia, rhabdomyolysis, hyperlipidemia, hepatomegaly, and renal failure. Early recognition is critical because it has a high mortality rate and treatment is fairly limited to supportive care and discontinuing propofol administration.

Benzodiazepines are GABA receptor agonists that produce anxiolysis at low doses and sedation, amnesia, and cardiorespiratory depression at higher doses. The most common benzodiazepines used in the ICU setting are midazolam, lorazepam, and diazepam. Both midazolam and lorazepam can be administered as continuous infusions, whereas all three can be administered intermittently and have rapid onsets of action. The duration of action for each of these drugs is relatively short on initial administration as they are lipophilic and readily distributed to peripheral tissues. However, repeated administration or prolonged infusions result in saturation of adipose tissues and prolonged sedation even after discontinuation. Age, obesity, and altered hepatic or renal function all can alter benzodiazepine clearance and must be considered when deciding on the appropriate medication. The side effects of benzodiazepine administration include cardiovascular and respiratory depression, delirium especially in the elderly, as well as propylene glycol toxicity. Propylene glycol is used as the solvent for IV lorazepam and diazepam, and toxicity is rare. It is characterized as an anion gap metabolic acidosis, renal failure, and eventual multisystem organ failure. Treatment is limited to dialysis and discontinuing the offending agent.

Dexmedetomidine is a centrally acting α2- adrenoreceptor agonist that binds to receptors within the locus ceruleus to provide sedation and anxiolysis and receptors in the spinal cord to provide for analgesia. It has a relatively quick onset of action between 5 and 15 minutes and a duration of action between 60 and 120 minutes. Dexmedetomidine is hepatically metabolized by glucuronidation and the cytochrome P450 system, and, as such, alterations in dosing may be required when other cytochrome P450 altering medications are being given. One of the main advantages of dexmedetomidine is that it has no effect on respiratory drive, so patients can be sedated without the need for mechanical ventilation. Studies have also demonstrated that dexmedetomidine usage results in extubation almost 2 days sooner compared to midazolam use. The adverse effects of dexmedetomidine use include bradycardia, hypotension, atrial fibrillation, and reflex hypertension with abrupt cessation of administration. Currently, the US. Food and Drug Administration (FDA) states the use of dexmedetomidine for initial sedation should be limited to 24 hours with the idea that prolonged use can exacerbate reflex hypertension when stopped.

It is not uncommon for ICU patients to receive continuous infusions of sedatives as it increases patient comfort and provides a reliable and consistent level of sedation. That being said, randomized trials have demonstrated that protocol-driven daily sedation interruption decreases the duration of mechanical ventilation and length of stay in the ICU and improves the ability to perform daily neurologic assessments. Sedation holidays are also cost-effective as they decrease amounts of medication administration and reduce unnecessary diagnostic testing obtained to evaluate a patient’s neurologic status.

Altered Mental Status and Delirium

Assessing and accurately diagnosing alterations in a patient’s mental status is an often overlooked and underestimated aspect of critical care. Alterations in mental status among the critically ill can be hard to recognize and include a spectrum of disorders including delirium, encephalopathy, and coma. Patients who are elderly and those with preexisting mental illness or cognitive impairment are at increased risk for developing alterations in mental status when critically ill. When a patient has an acute change in mental status, it is important to rule out any organic or potentially reversible causes because the diagnosis of delirium of critical illness is otherwise a diagnosis of exclusion. Some examples of organic causes that can lead to an acute change in mental status include hypoxia, hypercapnia, hypoglycemia, medication side effects or withdrawal, infection, metabolic derangements, cerebrovascular accidents, seizures, and changes in intracranial pressure.

When a patient becomes confused, they lose their sense of orientation and are no longer able to identify who they are or where they are and/or will lack a general perception of time. Delirium is defined as confusion along with a disturbance in focus, attention, or awareness that occurs over a short period of time. The delirious patient will also develop cognitive deficits such as memory loss and difficulty with language or visuospatial abilities. Identifying and trying to reverse the effects of delirium are important because those who develop ICU delirium have an increased mortality, residual functional disabilities, and higher rates of dementia after discharge. In general, hyperactive delirium is easier and more quickly detected as these patients are agitated and restless. However, the opposite is true for patients who develop hypoactive delirium, as they are quiet, inattentive, and lethargic, which can be easily overlooked and ignored. The elderly and patients with prior mental illness or decreased cognition are at higher risk for developing hypoactive delirium and should be evaluated carefully.

Assessment for delirium has been standardized by utilizing either the Confusion Assessment Method for the ICU or the Intensive Care Delirium Screening Checklist. Both assessment tools have been validated in the ICU setting and can also be utilized for the mechanically ventilated patient. Utilizing either one of these assessment tools on a regular and scheduled basis allows for an objective assessment of a patient’s mental status and increases the chances for early detection of delirium.

When a diagnosis of delirium has been established, prompt intervention is important in order to begin the process of reorienting the patient and identifying any precipitating factors. The basis of treatment includes identifying and reversing any potential organic causes and providing supportive measures that bring the patient’s behavioral alterations back to baseline. Supportive measures serve to limit abnormalities around a patient’s environment that would not necessarily be present and to provide a calm, secure, and safe environment. Modifiable behavioral and environmental factors include limiting circadian rhythm abnormalities and maintaining normal sleep-wake cycles by opening blinds or shades during the day and turning off lights at night, reducing ancillary and unnecessary noises or noxious stimuli, avoiding the use of restraints when safe, mobilizing the patient, providing the patient with their eyeglasses or hearing aids if needed, and having family or friends help to reorient and reassure the patient. New-onset delirium has been documented to result in a statistically significant increase in the 90-day mortality rate, which increased in a graded manner when these patients were exposed to noxious stimuli, placed in restraining devices, or developed hospital-acquired conditions such as falls or pressure ulcers. Altering a patient’s environment and normalizing their daily lives can be readily done and drastically affects mortality and outcomes.

If patient behavior interferes with their care or they are disoriented to the point of potentially harming themselves or others, low-dose antipsychotic medications such as haloperidol can be safely utilized. Benzodiazepine use should be limited to cases of sedative or alcohol withdrawal as they can precipitate delirium, especially in the elderly population. When sedative infusions are necessary, dexmedetomidine has been found to decrease the rate of delirium by more than 20% when compared to using midazolam, although no one agent is ideal and the proper choice of sedative needs to be made on a case-by-case basis. The medical workup of delirium should include a thorough review and cessation of any unnecessary medications, physical and neurologic examination with possible computed tomography (CT) imaging of the brain, and evaluation for potential infectious etiologies with sampling of cerebrospinal fluid with lumbar puncture when clinically indicated. If no obvious etiology is found, one must consider magnetic resonance imaging (MRI) of the brain, electroencephalogram, measuring drug or toxin levels, or prophylactic supplementation with vitamin B ¹² or folate if there is concern for alcoholism.

Often confused with delirium, which describes the mental manifestations of the disease, encephalopathy is a term to describe an altered mental state per the underlying pathophysiologic process. Encephalopathy develops as a syndrome of overall brain dysfunction and can occur from many organic and inorganic causes that directly induce brain injury or remotely affect the brain from other systemic causes. Encephalopathy can be described as acute or chronic based on the timing and potential reversibility of the syndrome. Chronic encephalopathy is slow to progress and results in structural changes in the brain that are usually irreversible. Acute encephalopathy can potentially be reversed with a return to baseline functional status if the inciting insult is removed or treated in a timely fashion. Examples of causes of encephalopathy include chronic traumatic encephalopathy, Wernicke-Korsakoff syndrome, heavy metal poisoning, electrolyte abnormalities, liver failure, medications, and sepsis.

At the furthest end of the spectrum of altered mental status is coma. A comatose patient is unarousable and unaware of their environment. Most cases of coma that present to the emergency department are due to trauma, cerebrovascular accidents, metabolic derangements, medications, seizures, and infections. The Glasgow Coma Scale (GCS) is a neurologic assessment tool that provides a reliable and objective measurement of a patient’s conscious state. It is composed of three elements (eye, verbal, and motor responses) and scaled from 3 to 15. The lowest possible score is 3 when a patient has no response to stimuli, and the highest possible score is 15 when a patient is fully awake and interactive. When comatose patients have a GCS score of 8 or lower, their brain injury or dysfunction is deemed severe and they should be intubated as they cannot reliably protect their airway. As is the case with most causes of altered mentation, treatment for a comatose patient is based on identifying and treating any reversible organic causes and providing supportive care.

Traumatic Brain Injury

One of the leading causes of disability in the United States, traumatic brain injury (TBI) is a devastating and life-altering event that often leads to heavy familial and socioeconomic burden. It is the most common cause of death and disability in people between the ages of 15 and 30, and the most severe cases result in prolonged periods of coma and unresponsiveness. The severity of TBI is classified using GCS scoring, as it is simple, reproducible, and a prognosticator for outcomes. Neuroimaging is utilized to identify pathologic injuries such as skull fractures, cerebral contusions, hemorrhage or hematoma, and diffuse axonal injury. Primary and secondary brain injuries are the two phases during which neuronal injury occurs. Primary brain injury occurs during the initial insult, whereas the focus of critical care management of TBI is to limit secondary brain injury. Secondary brain injury is a consequence of pathologic and physiologic alterations that manifest after the initial injury usually due to concomitant multiorgan injury. Examples of causes of secondary brain injury resulting in further neuronal injury and death include ischemia, hypoxia, hypotension, cerebral edema, acidosis, and elevated intracranial pressure.

Management and treatments are focused on optimizing intracranial pressure and blood pressure in order to maintain adequate cerebral perfusion, avoiding hypoxia, and maintaining normothermia and normoglycemia. Often, antiseizure medications are prescribed as antiseizure prophylaxis, although the ideal medication, dosage, and duration of treatment are not clearly established. Recovery after TBI can be a prolonged and lengthy process. Approximately 10% to 15% of patients with severe TBI (GCS <8) are discharged in a vegetative state, with approximately 50% regaining consciousness by 1 year. Medication adjuncts to accelerate and maintain long-term recovery are sparse. A randomized control trial investigating the use of amantadine has shown that, over a 4-week treatment period, patients showed accelerated recovery; however, over the long-term, there was no difference between the treatment and placebo groups. Long-term prognosis and recovery are variable and difficult to predict and are highly dependent on the severity of TBI, patient comorbidities, and postinjury complications.

Cardiac Physiology

The heart is a two-pump circuit in sequence. All blood that goes out of the right ventricle to the pulmonary circulation must then be pumped out of the left ventricle to the system circulation, with important exceptions that arise in the setting of congenital cardiac anomalies and a minor exception from bronchial arteries and veins. There is a vast difference in resistance between the pulmonary vascular bed faced by the right heart and the systemic vascular bed faced by the left heart, with the pulmonary pressures and resistance being significantly lower. The heart’s ultimate function is to supply oxygenated blood to the tissues of the human body. This ability is captured by the oxygen delivery (Do ₂ ) equation:

CO is defined as the blood flow put out by the heart per unit time, typically expressed in liters/min. An average, CO is 4 to 6 L/min. Overall, one observation is evident: the primacy of the hemoglobin and oxygen saturation in determining the carrying capacity of oxygen by the blood and the relatively trivial contribution of dissolved oxygen.

Vascular resistance is the collective resistance of all vessels including arteries and veins against the flow of blood, and there are two such resistances: the systemic vascular resistance (SVR) faced by the left ventricle and the pulmonary vascular resistance (PVR) faced by the right. The relationship between flow, pressure, and resistance is defined by Ohm’s law:

These relationships guide decisions about fluid and vasopressor therapy, which are elucidated later. The lower PVR consequently requires a smaller right heart muscle volume (lower pulmonary artery pressure) to supply the lungs with the same CO as the rest of the body. This means that the right heart is unable to maintain its CO in the face of large, acute rises in PVR, and this lack of reserve has significant consequences both in trauma surgery when a trauma pneumonectomy is performed and in thromboembolic disease in the lung. In both these situations, a sudden rise in PVR, particularly in the context of a low preload, can lead to cardiovascular collapse.

The heart muscle is supplied primarily by the coronary arteries. During systole, the subendocardial vessels experience retrograde flow, and thus the heart is primarily supplied during diastole. This has important implications for cardiopulmonary resuscitation, as failure to allow for full recoil of the chest may reduce blood supply to the subendocardium during resuscitation.

The heart’s rhythm is controlled by pacemaker cells. The primary node is the sinoatrial node, which is influenced by sympathetic stimulation from the sympathetic trunk mainly arising from the T1–T4 spinal levels, which stimulate positive chronotropy. Parasympathetic stimulation results in negative chronotropy and is mediated via the vagus nerve. The heart has a series of escape pacemakers, which are, in order, the atria, the atrioventricular node, and the ventricles themselves. As long as the sinoatrial node paces above the intrinsic rate of these escape pacemakers and as long as those impulses are transmitted through the atrioventricular node and to the ventricles, impulses from the sinoatrial node control the heart rate.

Cardiac Arrhythmias

Shock

The most severe hemodynamic alteration is shock, which is a condition of circulatory failure resulting in end organ dysfunction secondary to reduced perfusion. A shock state itself is indicated by signs of end-organ dysfunction such as rising lactate, altered mental status, falling urine output, and liver enzyme elevation. Each form of shock demands different responses, and when different forms of shock are combined, the appropriate management can be challenging. There are numerous forms of shock, classified broadly into four categories: distributive, hypovolemic, cardiogenic, and obstructive.

Myocardial Infarction

Both myocardial ischemia and MI are feared entities in the perioperative period, both of them portending significant morbidity and mortality. The lack of ischemic symptoms or electrocardiogram (EKG) changes associated with a rise in troponins is not a sign of safety, as mortality remains high. Two fundamental types of MI exist. Type I MI is based upon atherosclerotic plaque rupture, and consequent ischemia and infarction of muscle that was being supplied by that blood vessel. In contrast, type 2 MI is based upon a mismatch of the supply of blood and the heart’s demand for it and is also commonly referred to as demand ischemia. The treatments for each type of MI flow naturally from their causes: revascularization for type I MI and reduction of cardiac oxygen demand for type 2 MI.

Type 1 MIs can be broken down into ST elevation MI (STEMI) and non-STEMI (NSTEMI). As its name indicates, a STEMI classically involves symptoms and elevations in cardiac enzymes as well as evidence of ST elevations on EKG, while an NSTEMI is similar but without EKG evidence of infarction. Unstable angina is a symptom of ischemia, but without cardiac biomarker elevation indicating injury. These critical distinctions drive differences in the immediate management, and it should be noted that unstable angina and NSTEMI are indistinguishable in the first 6 hours as that is how long it takes troponins to become positive after cardiac injury. All three together form part of the spectrum of acute coronary syndrome.

The treatment of a type I MI in the postoperative period focuses on a percutaneous coronary intervention with thrombolysis as an option if timely percutaneous coronary intervention is unavailable. In NSTEMI, intervention can be delayed in some cases up to 72 hours. However, the overall intervention decision is complicated by the added burden of deciding on the risks and benefits of full-dose systemic anticoagulation in postoperative patients. In certain populations, such as those who recently underwent neurosurgical procedures, the risks of stroke or death from hemorrhage make percutaneous coronary intervention with its attendant anticoagulation unacceptable, while in other patients, the risks can be accepted.

In addition to the primary intervention, the complications of an acute MI must be managed. Cardiogenic shock should be managed as previously discussed. Nitroglycerin, either sublingual or IV, can be given for hypertension and for chest pain. The distinction between a right- and left-sided MI is critical, as giving nitroglycerin to reduce the afterload and myocardial oxygen demand in the setting of presumed left-sided MI may reduce the preload, resulting in right-sided heart failure if in fact the patient is suffering a right-sided MI. This could have catastrophic consequences. Pain control with any IV opiate such as morphine can be used to control chest pain symptoms if not relieved by nitroglycerin. The patient should be given aspirin and additional anticoagulant medications as specified by local protocol and depending upon the course of therapy chosen. Beta blockers should be initiated if there are no signs of cardiogenic shock, as these are cardioprotective. However, if the patient is hypotensive or has a decreased ejection fraction or bradycardia, avoid these. Above all else, have the defibrillator close by, pads preferably on the patient, ready to shock any life-threatening arrhythmias or pace the patient if they go into bradycardia secondary to heart block.

Respiratory Physiology

Respiratory physiology is characterized by two linked processes, oxygenation and ventilation. Oxygenation refers to the addition of oxygen (O ₂ ) to the blood stream from the air, which is typically at a concentration of 21%, also known as the fraction of inspired oxygen (FiO ₂ ). Ventilation is the clearance of carbon dioxide (CO ₂ ) from the blood stream, after the latter has been generated by cellular respiration. It can help to think of these two processes as entirely separate, although in reality, this abstraction breaks down at extremely low minute ventilations.

Both processes rely upon air coming down the oral cavity, into the trachea, through the bronchi and into the lung parenchyma, where blood brought from the pulmonary artery goes through the pulmonary capillaries. This alveolar-capillary interface is where gas exchange occurs. If too much blood flow relative to oxygenation capacity is present, it is referred to as shunt physiology. Air exchange in areas that do not have sufficient blood supply is known as dead space physiology. Some amount of both of these is normal: less than 10% of total CO does not participate in gas exchange and 20% to 30% of total ventilation does not equilibrate with blood. Increases in shunt fraction occur secondary to asthma, to distention of alveoli from pulmonary edema or pneumonia, to atelectasis, or to PE, where excessive CO flows through nonembolized regions. Dead space ventilation takes place when the alveolar-capillary interface is destroyed by emphysema, when the CO is low, or when air overdistends the alveoli during positive pressure ventilation. Oxygen delivery was previously discussed in the “Cardiovascular System” section and is not further discussed here.

In respiratory physiology, compliance is the increase in volume of a lung in response to a given pressure applied to it. Diseased, fibrotic lungs in interstitial lung disease or acute respiratory distress syndrome (ARDS) have low compliance. Critically, in the era of mechanical ventilation, low compliance can be a viscous cycle. An initial insult from pneumonia, pulmonary contusion, severe systemic disease like pancreatitis, or other cause can result in a decrease in compliance. Using mechanical ventilation, air is forced into the lungs to deliver a set amount of ventilation. This results in barotrauma, or trauma to the lungs from increased pressure. This barotrauma further decreases compliance. Thus, preventing barotrauma is a key goal of the ARDSNet protocol, which is discussed later.