Surgical Science and the Evolution of Critical Care Medicine : Critical Care Medicine

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CCM 50TH Anniversary Articles

Surgical Science and the Evolution of Critical Care Medicine

Ferrada, Paula MD, FACS, FCCM1; Cannon, Jeremy W. MD, SM, FACS2; Kozar, Rosemary A. MD, PhD, FACS3; Bulger, Eileen M. MD4; Sugrue, Michael MB, BCH, BAO, MD, FRCIS, FRACS A5; Napolitano, Lena M. MD, FACS, FCCM6; Tisherman, Samuel A. MD, FACS, FCCM3; Coopersmith, Craig M. MD, FACS, MCCM7; Efron, Phil A. MD, FACS, FCCM8; Dries, David J. MD, MSE, FACS, MCCM9; Dunn, Ty B. MD, MS, FACS10; Kaplan, Lewis J. MD, FACS, FCCP, FCCM2,11

Author Information
Critical Care Medicine 51(2):p 182-211, February 2023. | DOI: 10.1097/CCM.0000000000005708

Abstract

KEY POINTS

  • Questions: How has surgical science impacted critical care medicine as a field and Critical Care Medicine as a journal?
  • Findings: Surgical science in a host of areas has fostered improved patient care as well as scientific discovery in related fields and disciplines focused on providing critical care in and outside of a traditional ICU setting. Critical Care Medicine has served as a key venue within which to share surgical science in a global fashion with the broad critical care medicine community.
  • Meaning: Surgical science is broadly applicable to patient care regardless of practice focus and has shaped some of the evolution of Critical Care Medicine as a journal.

Landmark events in critical care medicine such as arterial blood gas analysis, invasive mechanical ventilation, and renal dialysis define key timepoints along the evolution to modern, complex, and multi-professional critical care. Advances across multiple disciplines have driven care innovations, enhanced understanding of disease-specific pathophysiology, and improved outcomes. This review explores those drivers as they relate to surgical disease management and their impact on critical care medicine as a discipline. Discoveries in ultrasound, resuscitation and coagulopathy management, endotheliopathy, Acute Care Surgery, open body cavity management, extracorporeal techniques, emergency preservation and resuscitation (EPR), the human microbiome, surgical infections, chronic critical illness (CCI), disaster management, and solid organ transplantation all influence management in ICUs around the world. Each of these domains has also impacted the content and trajectory of the Society of Critical Care Medicine (SCCM)’s flagship journal, Critical Care Medicine over the last 50 years. A hallmark aspect of critical care as a concept—and not a location—is that both knowledge and care approaches that blossom within one parent discipline readily find fertile ground within others to improve the care of the critically ill and injured. This article explores how key elements of surgical science have developed, shaped critical care across disciplines and locations, and specifically informed the readers of Critical Care Medicine as part of the journal’s 50th Anniversary celebratory series.

Point-of-Care Ultrasound

Originally, the sole purview of Radiology, trauma surgeons pioneered deploying bedside portable ultrasonography to rapidly and noninvasively detect free fluid in the peritoneal or pericardial spaces after injury; the specific examination was termed the Focused Assessment with Sonography in Trauma (FAST) (1–3). Later refinements expanded the FAST examination to the pleural space. This quiet revolution laid the foundation for a path toward point-of-care ultrasound (POCUS) in a host of hospital locations including the Emergency Department (ED), ICU, acute care floor, and Operating Room (OR) by practitioners of virtually every discipline. POCUS has been extended to the pleura as a diagnostic modality for pneumothorax or hemothorax, an evaluation of pulmonary parenchymal water during ventilator weaning, differentiating pneumonia from atelectasis, and, more recently, as a guide to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (4,5). Therefore, POCUS functions as an extension of the clinician’s physical examination to more precisely inform care decisions (6). Furthermore, POCUS enhances the safety of patient care during central venous line insertion—especially for trainees—and informs site selection in patients whose veins have been previously accessed (7). Similar safety benefits are noted during paracentesis and thoracentesis (8). Furthermore, POCUS performs equally well to CXR in identifying central venous catheter tip position and excluding pneumothorax (9). Ultrasound-guided peripheral vein access by bedside nurses in and out of the ICU is directly related to the acceptance of ultrasound as a tool that may be deployed by professionals outside of the Radiology Department (10).

POCUS is portable, repeatable, and safe and provides information that is immediately actionable (11–13). Nonetheless, POCUS accuracy and clarity are in large part operator-dependent. Training and practice are pivotal in ensuring device familiarity, for achieving reliable views and for correctly interpreting acquired data (14,15). Critical care POCUS often serves as a guide to intravascular volume during resuscitation from septic shock or hemorrhage, and provides a gross assessment of cardiac wall motion (16). Specific note is made of the plethora of acronyms that define protocolized examinations to guide resuscitation with no protocol demonstrating superiority (17–19). Although there was clarity around general POCUS competency and training requirements, cardiac-focused POCUS generated substantial controversy as ultrasound intruded into a closely regulated domain (20–23). In the mid-2000s, multiple statements appeared that addressed critical care ultrasound curriculum development as well as clinician competencies, including two in Critical Care Medicine (15,24,25). More recent multiprofessional collaborative efforts have defined a critical care echocardiography training and competency pathway, as well as a Board examination that is open to multiple disciplines (26). POCUS demonstrates the widespread adoption of a previously single discipline tool to support critical care regardless of location to establish key diagnoses, enhance safety, and improve survival especially during resuscitation from acute illness or injury.

Resuscitation and Coagulopathy Management

Acute hemorrhage remains the leading cause of potentially preventable death in injured patients, claiming nearly 50,000 lives in the United States and 1.5 million lives worldwide every year (27). Other patient populations who continue to suffer hemorrhage-related death include those with ruptured abdominal aortic aneurysms (10,000 U.S. deaths annually), peptic ulcer disease (nearly 2,000 U.S. deaths annually), and peripartum hemorrhage (140 U.S. deaths annually) (27). Other populations such as those with portal hypertension and esophageal varices, and those with more distal gastrointestinal (GI) track hemorrhage (dieulafoy lesions, diverticulosis, and aortoenteric fistula) are important groups who often require critical care and rapid resuscitation from hemorrhagic shock (28–30). Survival in these patients requires timely diagnosis, early hemostasis, and rapid targeted resuscitation in adults and pediatric populations alike (31–34). Patients with severe hemorrhage represent up to 16% of ICU patients with shock, with a substantial proportion of the remained demonstrating septic shock for whom initial crystalloid resuscitation remains appropriate and may be guided by measures of fluid responsiveness (35–37).

The management of patients with hemorrhagic shock—for whom resuscitation and hemorrhage control are immediate priorities—has substantially changed over the past 50 years (38–40). The lessons derived from a half-century of injured patient resuscitation include reduction in crystalloid volume, the development of hemostatic (aka. “damage control”) resuscitation to support coagulation integrity, and the utilization of massive transfusion protocols using 1:1:1 (packed PRBCs:fresh frozen plasma:platelets) ratios (41,42). Each of these approaches works together to improve injured patient survival but also benefits medical and nontrauma patient populations by prioritizing component transfusion coupled with rapid bleeding control (43,44). Although some of these approaches appear novel, others such as whole blood resuscitation are rooted in historic approaches to hemorrhage management and bring care full-circle (32,45–47). Damage control resuscitation, the current best practice, employs a system approach to mitigate both host and iatrogenic contributors to hypothermia, acidosis, and coagulopathy (48,49). Emphasis has shifted away from crystalloid and colloid-based resuscitation to balanced blood components or empiric, initial whole blood transfusion that is further refined by viscoelastic hemostatic assay results (39,45,46,50,51). Damage control resuscitation often leverages nonsurgical hemostatic agents, including topical powders or sprays, that are also used as hemostasis adjuncts for endoscopic control of GI hemorrhage (52,53). Furthermore, different coagulopathy phenotypes may warrant nuanced resuscitation approaches (54). Relatedly, a coagulopathic phenotype in sepsis patients has been recently described using transcriptomic analysis (55). Importantly, induced coagulopathy correlates with mortality after injury or sepsis, as well as thromboembolic event risk (56–58). Identifying the acute coagulopathy of trauma dovetails with coagulopathy investigations in other settings including extracorporeal membrane oxygenation (ECMO) and SARS-CoV-2 infection, specifically addressing molecular and viscoelastic profiles (59,60). IV pharmacologic adjuncts play a complementary role in coagulopathy management as well. For example, vasopressin infusion demonstrates a component transfusion sparing effect; the role of other vasopressors remains controversial (61–63). Calcium supplementation is a key component of coagulopathy abrogation in all settings that employ massive transfusion for resuscitation from hemorrhagic shock (64).

Achieving normothermia coupled with acidosis and coagulopathy resolution remain reliable goals prior to planned reexploration after a damage control laparotomy that controls acute bleeding and GI tract soilage (38,39,65,66). Failure to achieve these objectives often indicates ongoing hemorrhage, or persistent malperfusion, each of which warrants unplanned return to the OR. Evolving end points that signal successful hemorrhagic shock resuscitation help inform the timing of planned reexploration for definitive surgical management and help avoid postsurvival complications such as multiple organ failure (67,68). Developing approaches to more precisely guide timing include decision support tools to facilitate optimal resuscitation; in silico modeling to plan clinical trials, novel monitoring, and management strategies such as microcirculation dark field microscopy, and trigeminal nerve stimulation (69–72). Perhaps most importantly, each of these approaches is not solely applicable to surgical patients. Instead, like the tenets of hemorrhagic shock resuscitation that evolved following both civilian and military injury management, these emerging techniques are anticipated to be broadly applicable to those requiring resuscitation and coagulopathy management regardless of underlying etiology. A related link between multiple disciplines and patient types is the underlying pathophysiology of many forms of coagulopathy—endotheliopathy.

Endotheliopathy

Recognizing that plasma transfusion may provide more benefits to hemorrhagic shock patients that solely repairing acute coagulopathy as part of damage control resuscitation established the conceptual framework for the endotheliopathy of trauma (EOT) (73,74). The EOT reflects a systemic response to injury including deranged coagulation, inflammation, and endothelial barrier integrity (75). Accordingly, plasma transfusion in conjunction with valproic acid improves blood-brain barrier function after traumatic brain injury (76). Clinically, EOT manifests as a proinflammatory state with vascular leak and tissue edema, which exacerbates postinjury organ failure and death. With syndecan-1 as its core protein, the glycocalyx shields the underlying endothelium from injury during homeostasis. However, following hemorrhagic shock, sepsis, or critical illness, the syndecan-1 ectodomain is shed, leaving an exposed and vulnerable endothelium (77–79). Endothelial injury leads to inflammation, vascular leak, and abnormal coagulation (80). This linked process is similarly identified in pediatric extrapulmonary sepsis patients and is associated with developing early acute respiratory distress syndrome (81). Patients with traumatic hemorrhagic shock demonstrate microcirculatory failure that is identifiable using sublingual microscopy and correlates with organ failure (71,82). Unsurprisingly, syndecan-1 shedding as a reflection of endothelial damage independently predicts postinjury mortality (83,84). Thus, syndecan-1 has become the most intensively investigated biomarker for the EOT (85). In addition to syndecan-1, von Willebrand’s Factor (VWF) is increasingly recognized as a key EOT mediator (86). It is secreted by endothelial cells after injury in a pathologic, multimeric, and hyperadhesive form whose generation stems from a decrease in its cleaving enzyme, ADAMTS13. The imbalanced ratio of VWF to ADAMTS13 additionally drives the coagulopathy of EOT (87,88). Similar findings have been noted regarding SARS-CoV-2-associated thrombosis—a line of inquiry related to the early investigations that established the EOT (89). Furthermore, decreased ADAMTS13 activity is implicated in the untoward outcomes of patients with sepsis-associated organ failure, helping establish a pathogenetic pathway linking infection, host response, and organ impact (90).

In addition to syndecan-1 shedding, endothelial syndecan-1 messenger ribonucleic acid (RNA) is also reduced following shock in part due to a recently identified endothelial microRNA, microRNA-19b (91). This microRNA degrades syndecan-1 messenger RNA by specifically binding to its 5’ untranslated region, contributing to postshock inflammation, organ injury, and enhanced permeability. Fibrinogen has been shown to both inhibit this pathogenic microRNA and bind to syndecan-1 on the endothelial cell surface restoring endothelial barrier integrity (92,93). Fibrinogen also possesses antiapoptotic properties that further enable endothelial protection (94). The early use of plasma following hemorrhagic shock delivers fibrinogen as a major protein component and improves outcomes (95). This outcome benefit—besides plasma volume expansion and clotting enhancement—is believed to be related to endothelial protection through endothelial syndecan-1 restoration (96). Other transfusion-related studies also demonstrate improved outcomes and decreased EOT, primarily while assessing the transfusion of fibrinogen or cryoprecipitate (97–99). Recently, burn sepsis and its related vascular dysfunction are well identified using protein biomarkers that reflect endothelial failure including syndecan-1, p-selectin, and galectin-1 (100). Indeed, the SCCM’s Research Section articulated a variety of translational research opportunities related to SARS-CoV-s infection for which endotheliopathy provided a cornerstone (101). Component transfusion therapy as an endothelial therapeutic following hemorrhagic shock appears relevant for other disease states such as adult and pediatric sepsis, traumatic brain injury, SARS-CoV-2 infection, and burns (102). Therefore, specific avenues of scientific inquiry initially related to coagulation failure after critical injury has informed and shaped inquiries into diverse aspects of critical illness.

Acute Care Surgery

Acute Care Surgery is a subspecialty of General Surgery, which includes a primary focus on advanced trauma and emergency general surgery coupled with surgical critical care; many practitioners also maintain an elective practice (103,104). Subspecialty certification in Surgical Critical Care was established by the American Board of Surgery in 1987. In the 1990s, increased nonoperative management of injuries raised the concern that a primary surgical critical care practice would not be attractive to graduating general surgery residents, and that practicing surgeons would risk skill atrophy. Relatedly, in 2006, 40% of Surgical Critical Care (SCC) fellowship positions went unfilled due to insufficient applicants. As a result, the specialty of Acute Care Surgery was defined by the American Association for the Surgery of Trauma (AAST) and postresidency Acute Care Surgery fellowship programs were developed to augment existing SCC fellowships (105). Furthermore, the evolution of Acute Care Surgery services without a vast expansion in the clinician pool drove uncertainty around the physician staffing of specialty ICUs, and highlighted the value of nonsurgical intensivist partners, as well as Advanced Practice Providers (APPs), in providing surgical ICU care (106). The first AAST approved Acute Care Surgery fellowship launched in 2008 and has resulted in a steady increase in applicants for SCC certification. In 2020, only 15% of SCC fellowship positions were unmatched despite a doubling of training positions over the last 10 years (107).

Simultaneously, state and regional trauma systems have been evolved that concentrate on high-acuity injured patients in level I and II trauma centers where Acute Care Surgery surgeons provide 24/7 in-house call coverage. Many centers have since adopted an Acute Care Surgery practice model establishing a service, which is staffed to provide continuous coverage for surgical emergencies and provide surgical critical care in the ICU. Service expansion and the need for patient care have also driven the incorporation of APPs into service lines in the ICU, the acute care floor, as well as the clinic (108). Training centers that house surgical critical care and ACS fellowships increasingly deploy APP fellowships as well help supporting the increasing need for APP team members across ICUs of varying specialties (109). ACS services reduce the time to operative intervention for patients with surgical emergencies and improve outcomes spanning acute cholecystitis, intestinal obstruction, as well as necrotizing soft-tissue infection (NSTI) (110–112). In particular, NSTI care benefits from a team-based approach in the ICU (113).

Failure to Rescue has been adopted as an important assessor of hospital quality across a number of disciplines. The ICU is where patients go for rescue or receive care after undergoing the initial rescue efforts in locations such as the OR. The Failure to Rescue rate is determined by the mortality rate in patients suffering specific inhospital complications based on diagnosis (114). Thus, the concept of surgical rescue serves as an added benefit of deploying an ACS service that enables care throughout the facility and complements existing Rapid Response Team activities (115–117). By having experienced surgeons in the hospital 24/7, ACS surgeons play a unique role in ensuring optimal surgical care for patients presenting through the ED, as well as inpatients suffering unexpected events on the acute care floor, or the Medical ICU (118). One example is the development of innovative approaches to managing patients with toxic megacolon secondary to Clostridium difficile (119,120).

Specific resource needs for ICUs caring for Acute Care Surgery patients—including those after surgical rescue—have been assessed and are increased compared with other ICUs. These resource needs may reflect posturgent surgical care needs as well as increased rates of patient transfer for patients requiring complex acute care (121). In fact, nearly one quarter of patients transferred for complex care underwent an antecedent surgical procedure (122). Additional system-level analysis is defining the regionalization of care for complex critically ill patients to ensure optimal outcomes—a process driven in part by the development of Acute Care Surgery services that provide rescue not only in the hospital but across a geographic service area (123,124). The evolution of Acute Care Surgery has augmented surgical critical care by defining a specialty that attracts more surgeons to the field, improves the time to operative intervention and the quality of care for critically ill patients, and provides continuous coverage by specifically trained surgeons to support surgical rescue for the hospital and the regional healthcare system, while driving research to advance care. A major research domain has been intra-abdominal hypertension and the Abdominal Compartment Syndrome.

Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome

Early recognition of the consequences of pressure-volume dysregulation arose during attempts at closure after trauma laparotomy. This recognition led to intra-abdominal packing and a “damage control” approach to injury care that arrested major hemorrhage, controlled GI perforation, and leveraged an open abdomen approach to truncate OR time, and achieve expeditious ICU admission for rewarming, resuscitation, and metabolic rescue (125). The notion of intra-abdominal hypertension (IAH) as a pathologic process that could also lead to organ injury and failure defined a syndrome termed the Abdominal Compartment Syndrome, akin to a similar syndrome in the extremities that followed ischemia and reperfusion, or injury-associated intracompartment hemorrhage. IAH was formally defined in 2001 and led to the formation of the World Society of the Abdominal Compartment Syndrome (WSACS) in 2004; IAH was defined as an intra-abdominal pressure (IAP) greater than 12 mm Hg. The Abdominal Compartment Syndrome was defined as an IAP greater than 20 mm Hg with an attributable organ failure. In a fashion similar to ICU care, WSACS crafted multiprofessional guidelines to both medically and surgically addressed Primary, Secondary, Tertiary (recurrent), and, more recently, quaternary Abdominal Compartment Syndrome (126). The frequency and outcomes of IAH management were assessed to draw attention to guidelines in both medical and surgical ICUs (127). Importantly, despite clinical recognition of the consequences of IAH and the Abdominal Compartment Syndrome, few intensivists previously demonstrated working knowledge of either entity (128). This knowledge gap spurred basic investigations focused on the kidneys and the onset of acute kidney injury as a rapidly impacted organ with increased IAP; the small bowel mucosa seemed less impacted (129,130). These knowledge gaps were addressed with focused reviews addressing both medical and surgical populations—especially during the time period when Early Goal Directed Resuscitation was changing the initial resuscitation volume when treating sepsis and septic shock (131,132). It was during this period that hemorrhagic shock resuscitation pivoted away from crystalloids to instead leverage component transfusion therapy and avoid promoting ascites and the secondary Abdominal Compartment Syndrome (133,134). The damage control approach was soon extended to include patients cared for by Acute Care Surgery services to address IAH and the Abdominal Compartment Syndrome in those critically ill patients as well (135). Relatedly, IAH and the Abdominal Compartment Syndrome impacted critically ill children in a similar fashion (136).

Forward looking notions of space travel prompted investigation into the impact of weightlessness on IAH (137). Combined efforts at care refinement defined standards for IAP measurement and defined how IAH confounds measures of fluid responsiveness (138,139). As a result of combined educational efforts and algorithm implementation approaches, mortality from IAH and the Abdominal Compartment Syndrome improved as did survival to hospital discharge (140). At present, Abdominal Compartment Syndrome is less common in nontrauma populations than in the early 2000s, but IAH remains quite common—30% of mixed medical-surgical patients on ICU admission, and additional 15% develop it during care, but only 3% demonstrate the Abdominal Compartment Syndrome (141). These benefits have accrued from revised guidelines, updated reviews, bringing the surgical team to the ICU bedside instead of the patient to the OR, as well as refreshed implementation approaches that crossed specialty boundaries (142,143). Ongoing multicenter inquiry is further refining how patients with IAH or the Abdominal Compartment Syndrome are optimally managed including which patients benefit from an open abdomen approach (144).

Extracorporeal Techniques

Initially related to the heart-lung bypass machine, extracorporeal life support (ECLS) techniques are increasingly used to rescue our most critically ill patients in the ICU from respiratory and cardiac failure; ECMO centers continue to increase in number as a result. Related extracorporeal techniques include continuous renal replacement therapy (CRRT) for acute kidney injury management and support systems for acute liver failure. Additional extracorporeal rescue therapies for septic shock and cytokine release syndrome include hemoperfusion and hemadsorption for cytokine bioburden reduction (145). These extracorporeal technologies increasingly help save the lives of critically ill and injured patients as part of an expanded armamentarium of therapies. As a pioneer surgeon and surgical intensivist, Robert H. Bartlett, MD, is the leader in the laboratory development and refinement of ECMO for human use, treating the first adult with severe hypoxemia after injury in 1972, and the first neonate with meconium aspiration in 1975 (146–148). Venovenous ECMO for severe adult respiratory failure rescue has vastly expanded since the 2009 influenza pandemic, with improved outcomes related to smaller circuits, and deployment of single dual-lumen cannulas to allow patients to be awake, ventilator liberated, ambulating, and with decreased anticoagulation requirements. Recent investigations detail changes in platelet phenotype that may influence bleeding risk and inform anticoagulation strategies (149). Both thrombosis and hemorrhage are risks with ECMO therapy and appear to be accelerated by the underlying disease process (150,151). Nonetheless, a liberal transfusion threshold did not improve outcomes but did increase resource utilization and, therefore, cost (152). Venoarterial ECMO use for adult cardiac failure, refractory septic shock, and extracorporeal cardiopulmonary resuscitation (ECPR) are all also increasingly used (153). Nonetheless, differences in brain injury have been identified when comparing ECMO modalities that may reflect patient acuity and specific rescue needs (154).

Relatedly, the articulation of ECMO rescue teams to bring therapies to patients too unstable to travel has expanded access to life-saving therapy by both ground and air ambulance modalities (155). ECMO survival rates have increased, with survival for adult pulmonary ECLS 66%, adult cardiac ECLS 59%, and ECPR 41% from the April 2022 ELSO Registry Report; pediatric and neonatal ECLS survival rates are even higher including when used to help manage pediatric poisoning or stem cell transplantation (156–158). The number of ECMO centers has also increased significantly from 150 in 2008 to over 500 in 2022, paralleling the increase in indications, as well as dwindling contraindications for ECLS approaches including as a bridge to Left Ventricular Assist Device placement for cardiogenic shock management or pulmonary embolism rescue (159–161). ECMO techniques benefit from specific ventilator prescription to reduce pulmonary biotrauma (162). Similarly, added benefit is described for prone positioning in combination with ECMO rescue for severe COVID-19-associated respiratory failure (163). Importantly, intensivist-led cannulation programs increasingly flourish in an ECMO supportive environment, and specific intensivist roles have been defined (164,165). Thus, ECMO has moved from the exclusive purview of cardiothoracic surgeons to other specialties skilled in percutaneous vascular interventions, including within military air transport that support combat casualty care (166,167).

As an extracorporeal technique, ECMO dovetails with early pioneering efforts in the development of CRRT and extracorporeal liver support for patients with acute kidney injury or hepatic failure (168–170). Recently, CRRT has been coupled with extracorporeal CO2 removal reflecting continual innovation in device development and coupling (171). Additionally, similar to ECMO patient mobilization, CRRT patient mobilization is also well studied and safe, challenging preconceived notions permeating ICU patient care (172). With randomized trial data, selecting the most appropriate mode—and time of initiation—for kidney replacement therapy for the critically ill has been clarified, with intermittent hemodialysis (IHD) techniques emerging as appropriate for most; CRRT remains targeted to patients with hemodynamic lability and vasopressor infusion (173). Although IHD and CRRT use is quite common in the ICU, extracorporeal liver support is less readily accessible (174,175). An emerging concept is modular extracorporeal organ support (ECOS) therapy that simultaneously supports multiple failing organs (cardiac, respiratory, renal, hepatic), rather than using multiple single-organ support systems (176). ECOS therapy warrants rigorous study but was recently considered for critically ill COVID-19 patient rescue (177). The panoply of extracorporeal support technologies that have blossomed from the early heart-lung bypass machine spans the range of intensivist specialties and aligns well with providing optimal care to the critically ill and injured.

Emergency Preservation and Resuscitation

Patients who suffer a cardiac arrest from exsanguinating injury and undergo aggressive resuscitation, including a resuscitative thoracotomy, have a less than 10% chance of survival (178–181). Novel therapies are clearly needed to improve such dismal outcomes. An initial approach was termed “suspended animation” and outlined key elements of a rescue approach for those with exsanguinating hemorrhage including metabolic management of organ function, circulatory arrest, induced hypothermia, and control of injury in a bloodless field (182,183). Animal model success was key in laying the foundation for later human trials (184). Such an approach is needed because with certain injuries, surgeons cannot stop the bleeding quickly enough to facilitate restoration of spontaneous circulation and prevent organ injury and subsequent multiple organ failure (185). Additionally, operative control of injury may be complicated by acute coagulopathy, impeding the success of mechanical repair techniques. Recently, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), Selective Aortic Arch Perfusion (SAAP), ECLS, and EPR have emerged as potential interventions for trauma victims presenting “in extremis” and also have their roots in successful animal models (186,187). Some of these therapies are related to early explorations of hypothermia in the setting of cardiac arrest that led to current management strategies that improve postresuscitation neurologic outcomes (188–190). These data include both adults and children and embrace extracorporeal techniques to supplement targeted temperature management (191). EPR, the most invasive of these novel therapies, may have particular applicability in the setting of major noncompressible hemorrhage when REBOA, SAAP, and ECLS are not applicable or ineffective. The concept of EPR is to rapidly decrease metabolic rate to protect vital organs until hemostasis, and delayed reperfusion can be achieved. Animal studies demonstrate that pharmacologic approaches seem to have minimal impact on outcome (192–194). On the other hand, rapid cooling of the whole body during a prolonged period of circulatory arrest followed by delayed resuscitation using full cardiopulmonary bypass (CPB) is feasible, at least in animal models (195). More importantly, this approach can allow neurologically intact survival after as long as 3 hours of no blood flow in relevant animal models (196–198). Most importantly, clinically relevant injuries can be repaired during the period of hypothermia and no blood flow (197,198).

The Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma trial has been developed and initiated at the University of Maryland Shock Trauma Center based on these preclinical data (199). Potential subjects must be 18–65-year-old victims of penetrating injury who have suffered a cardiac arrest shortly before hospital arrival, in the ED, or in the OR. If they do not quickly regain a pulse after standard resuscitation efforts, including a thoracotomy with cross clamping of the descending thoracic aorta, and all the necessary personnel are available, EPR may be initiated by advancing a CPB cannula directly into the aorta proximal to the level of the cross clamp (Fig. 1). Ice-cold saline is rapidly infused until tympanic membrane temperature decreases to 10–15°C. The right atrial appendage is opened to allow venous drainage. Once the goal temperature is reached while in the ED, the patient is transported to the OR while pulseless. In the OR, a trauma surgeon focuses on injury control (especially those associated with hemorrhage), and a cardiac surgeon centrally cannulates for full CPB. Resuscitation and slow rewarming may be then initiated. Patients who meet the EPR inclusion criteria at a time when the necessary personnel for EPR are not all available serve as concurrent control patients (Fig. 2). The primary end point is survival to hospital discharge without major neurologic deficits. Secondary end points include survival to 28 days, neurologic functional outcome (Glasgow Outcome Scale-Extended, 36-item Short Form survey) at 6 and 12 months, organ failure, and technical complications. This initial safety and feasibility study targets 10 EPR subjects and 10 control subjects. If EPR proves feasible, it may become part of a novel and universal strategy for the management of the exsanguinating trauma patient that may also include REBOA, SAAP, and ECLS (Fig. 3) (187). Similar to ECMO cannulation that is undertaken by clinicians other than surgeons, this approach offers a similar future potential as well. Importantly, this kind of innovative science represents the culmination of decades of preceding work that dovetails with community-based research disclosure that leads to exemption from informed consent—a formidable undertaking (200,201).

F1
Figure 1.:
Emergency preservation and resuscitation. Hypothermia is induced by large-volume cold fluid infusion into the thoracic aorta with the right atrial appendage vented to allow drainage and avoid overdistension. Reproduced with permission from Manning et al (187). RA = right atrium.
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Figure 2.:
This graphic denotes the currently approved Emergency Preservation and Resuscitation study algorithm. Reproduced with permission from Manning et al (187). CPB = cardiopulmonary bypass, ED = emergency department, EPR = emergency preservation and resuscitation, OR = operating room.
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Figure 3.:
An integrated approach to deploying Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), Selective Aortic Arch Perfusion (SAAP), extracorporeal life support (ECLS), and emergency preservation and resuscitation (EPR) in the treatment of severe uncontrolled hemorrhage based on the needs of the injured patient and response to therapy. Reproduced with permission from Tisherman et al (199). NCTH = noncompressible Torso hemorrhage, ROSC = return of spontaneous circulation, V-A = venoarterial.

Microbiome and Gut Permeability

Under basal conditions, there are 40 trillion microbes residing within the intestinal lumen—at least as many microbes as there are host cells, with nearly 100 times the number of genes (202). Critical illness is associated with profound changes in the microbiome within hours of the initiating insult. Seminal work demonstrates that, in critical illness, the microbiome is transformed into a pathobiome that is detrimental to the host (203). The pathobiome is characterized by a loss of commensal organisms with a rise in pathogenic phyla accompanied by the induction of virulence genes. The pathobiome has been robustly explored in the context of GI anastomotic failure, extending novel surgical discoveries to a variety of nonsurgical conditions (204,205). The robust diversity of the healthy microbiome containing approximately 1,000 different bacterial taxa is lost and replaced in subsets of patients by ultralow diversity pathogens that can sense host stress and upregulate native virulence factors (206–209). This transition is associated with higher morbidity and mortality in ICU patients (210). Accordingly, understanding and leveraging the microbiome have been identified as a priority in sepsis-driven research (211). Multiple interdigitating mechanisms may induce the pathobiome. Critical illness, regardless of specific etiology, induces rapid and maladaptive changes to the microbiome as well as gut permeability. In addition, these changes are exacerbated by treatments intended to improve patient-centric outcomes in the ICU including antibiotics, opioid analgesics, vasopressors, proton pump inhibitors, as well as the route of nutritional support, or the absence of nutritional substrate (212–214). Relatedly, the method of nutritional support (oral, enteral access catheter, and parenteral) influences gut blood flow with parenteral nutrition, decreasing superior mesenteric artery flow and enteral supplementation increasing flow (215).

The pathobiome has long been hypothesized to play a direct role in mortality from critical illness, as opposed to simply being an epiphenomenon. Preclinical modeling demonstrates that genetically identical mice with distinct microbiomes have different mortalities when subjected to intra-abdominal sepsis; animals with greater microbiome diversity demonstrate improved survival (216). Improved survival is associated with increased effector and central memory T cells in animals with a more diverse microbiome. Notably, when animals with different microbiome diversity indices were cohoused—and developed a similar microbiome—all survival and immunological differences disappeared. Multiple bedside approaches have been deployed to target the microbiome including probiotics, prebiotics, synbiotics, fecal microbial transplantation, and selective decontamination of the digestive system (217–223). Although results of these have been mixed, the gut microbiota remains a target of robust clinical research to improve outcomes in critical illness. Indeed, microbiome alterations, especially in the setting of multidrug-resistant organisms, play a key role in nosocomial infection (224,225). An important mechanism that explains the influence of the microbiome on infection, critical illness, and outcomes relates to gut permeability and bacterial access across the gut mucosal barrier. Recently, neuroinflammation in patients with sepsis has been linked to gut microbiota, indicating the remote impact of altered local host barrier competency (226).

The intestinal epithelium is a single cell layer, which separates the host from the microbiome that resides within the gut lumen. Under basal conditions, the gut mucosal barrier allows paracellular movement of water, solutes, and immune modulating factors while preventing bacteria from invading the host (227). Gut barrier function is mediated in part via the apical tight junction (TJ), which is functionally and structurally linked to the perijunctional actin-myosin ring (228). TJs alter paracellular movement via two distinct pathways. Only small molecules can pass through the pore pathway (<8 Å), whereas larger molecules such as lipopolysaccharides can pass via the leak pathway (<100 Å) (229,230). In addition, a third TJ-independent unrestricted pathway, which does not have a size limit, occurs at sites of epithelial damage and apoptosis, and bacteria can only cross the epithelium via this pathway (227). Critical illness and infection, in particular induce intestinal hyperpermeability, and this is associated with worsened outcomes (231,232). Preclinical studies demonstrate that depending on the model used and portion of the gut sampled, alterations in intestinal claudins 1, 2, 3, 4, 5, and 8, occludin, Junctional Adhesion Molecule-A and phosphoprotein ZO-1 occur as early as 1 hour after the onset of sepsis, supporting the need for rapid resuscitation and viewing sepsis as an emergency (233). Additionally, overexpression of the antiapoptotic protein Bcl-2 in the intestinal epithelium in septic mice decreases programmed cell death, which in turn normalizes gut permeability to levels seen in sham mice and is associated with alterations in claudins 3, 4, and 5 (234). Further, myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in contraction of the actin-myosin ring and increased permeability at the cell-cell junction (235). Clinically relevant, bacterial infection activates MLCK, inducing alterations in TJs and production of proinflammatory cytokines (236,237). Notably, MLCK−/− mice have improved survival following intra-abdominal sepsis, suggesting that targeting permeability is a therapeutic option in critical illness and may be explored using surgically relevant models (238). However, adminstering an inhibitor of MLCK paradoxically worsened intestinal permeability and mortality in septic mice, demonstrating the complexity of attempting to translate this approach to patients (239). Microbiome alterations and gut permeability are two commensals of most major surgical infections and their management.

Surgical Infections

Surgical infection management often intertwines with sepsis management (240). Although sepsis and septic shock definitions have evolved, their relationships with surgical infections remain firm (241,242). The care of hospitalized patients with surgical infections demonstrates broad overlap with the Surviving Sepsis Campaign guidelines for therapy as well as their implementation bundles (243–250). Indeed, each of the Surviving Sepsis Campaign guidelines reinforces the need for source control of loci of infection when there is a source controllable lesion—a task clearly easier to accomplish when there is an abscess or intestinal perforation than when there is cellulitis or pneumonia (251). The time-sensitive nature of source control reflects the time-sensitive nature of sepsis and septic shock, in particular, in the ED, OR, and ICU with early antibiotics and adequate source control reducing mortality (252,253). Relatedly, patients with infection who need surgical management or those who have had surgery and need a second procedure (operative or interventional radiologic) to control infection have helped drive the evolution of Acute Care Surgery services, and the use of damage control techniques to achieve rapid source control explored above (254). Furthermore, necrotizing infections (necrotizing cellulitis, fasciitis, myositis, or vasculitis) are similar to intestinal ischemia in that trying to achieve successful pre-operative resuscitation is ineffective regardless of resuscitation approach and only delays potentially life-saving source control (255,256). Accordingly, soft-tissue infections accompanied by sepsis or septic shock provide a springboard from which to assess the impact of source control on outcomes (257). Unsurprisingly, the rapidity of securing source control aligns with improved outcomes. Once admitted to the ICU, clinical practice guidelines for patients with surgical infections also improve outcomes by reducing variations in care, as well as by decreasing antibiotic duration and therefore cost (258). Guideline-driven care strongly supports antimicrobial stewardship for those with critical illness or injury in ICUs regardless or patient type (259,260). Antimicrobial stewardship’s role in reducing multidrug-resistant organism induction and ensuring that prescribed therapy aligns with culture data is so important that it is one of the next five Choosing Wisely Campaign critical care recommendations developed by the SCCM (261).

Although control of surgical infection relies on resuscitation, antibiotics, and source control, control of inflammation may also be important, an approach termed inflammatory source control. This approach has been best explored after thermal injury where burn wound inflammation reduction appears to improve pulmonary function and survival (262). The importance of this surgically relevant investigation is that it ties into current notions of cytokine storm and the benefits of its control within the context of acute SARS-CoV-2 infection—the recognition of which led to glucocorticoid therapy for rescue (263). The interplay of native immunity and recovery after surgical infection is both complex and incompletely understood. Recent investigations assessing the impact of aging on native immune system competence demonstrate adverse effects on inflammation reduction, organ function, and immune competence (264). These discoveries reinforce existing notions regarding acquired immune paralysis—especially in the elderly—as well as in those with injury, malnutrition, or sepsis (265). Patients with any of those conditions often demonstrate maladaptive and persistent inflammation underpinned by similar immune system defects. The homogeny of immune signatures has been similarly noted when comparing patients with sepsis, injury, or postsurgical states compared with healthy volunteers (266). Although the initial immune profiles were quite similar across the patient groups, a subgroup of the severely injured demonstrated delayed and acquired immunodeficiencies that correlated with an increased risk of secondary infection. Importantly, patients who demonstrate abnormal inflammatory profiles as well as prolonged ICU stay, persistent organ failure, and a high predilection for recurrent infection define a rapidly increasing patient population beleaguered by chronic critical illness (CCI).

Chronic Critical Illness

Through improvements in early sepsis detection and acute ICU management, most patients now survive their initial injury, septic insult, or other index admission condition. Many reestablish physiologic homeostasis and exhibit uncomplicated clinical trajectories. However, a significant number of individuals do not rapidly recover but are left to endure prolonged and complicated ICU stays, permeated with significant morbidity or mortality (267,268). Initially described after surgical sepsis, this condition has been termed CCI and occurs in patients demonstrating prolonged acute- and chronic-care hospitalization (ICU stay > 14 d), recurrent infections, and nonresolving organ dysfunction in adults and children including those with chronic illness and prolonged ICU care (269–271). In 2009, patients admitted to the ICU who developed CCI accounted for over $20 billion dollars in healthcare costs (272,273). The majority of these patients (>60%) were admitted with a sepsis diagnosis (272). Most recently, that while accounting for just 5% of ICU admissions, patients with CCI accounted for greater than 30% of ICU bed days and greater than 14% of hospital bed days, demonstrated higher mortality, and were less likely to be discharged home, extending the exploration of CCI to other patient populations (274). Data from surgical ICUs reveal that up to one third of critically ill patients who survive will develop CCI (269,270). Importantly, approximately half of these surgical sepsis survivors who develop CCI die within 1 year. CCI survivors often suffer moderate disability and fail to recover to their baseline level of health (268–270). This contributes to the burdens borne by uncompensated caregivers as well as postcritical care financial toxicity (275). Both of these aspects of CCI bear broad overlap with the Post Intensive Care Syndrome-Family that afflicts family members of critical illness or injury survivors (276).

The current CCI epidemic represents a new and difficult scientific challenge (277). CCI and its bleak long-term outcomes occur in a diverse patient population whose characterization requires both inhospital and long-term posthospital discharge follow-up, some of which may occur in post-ICU clinics (278–280). Such clinics are increasingly common in the wake of acute SARS-CoV-2 infection as well as the development of “long-COVID” and its impact on frailty, disability, and persistent breathlessness (281–283). Importantly, while not all postintensive care syndrome patients have CCI, the majority of CCI survivors are likely to have the postintensive care syndrome. Although these assessments are essential in elucidating CCI’s debilitating outcomes, multiple comorbid diseases make a definitive, clinical, and mechanistic investigation difficult (284,285). These obstacles serve to confound delineating the natural history of CCI survivors. In addition, the elderly seem to be at particular risk for CCI regardless of whether hospitalization is related to injury (277,286). CCI, therefore, must be studied at multiple levels, including within the clinical, translational, and basic science domains (287–289). Nonetheless, the CCI patient population raises important concerns regarding ethics, the delivery of goal concordant care, and the role of surrogate decision-makers, especially since family/decision-maker and care team conflict often permeates major care decisions for complex patients (290–292). These concerns have also helped shape ethics related to crises and disasters, some of which helped guide triage and care decision-making during the recent pandemic (293–295).

Disaster Management

Disasters or crises may be naturally occurring or manmade. Individuals—including lay persons—as well as hospitals, hospital systems, public health agencies, Emergency Medical Services, law enforcement, and fire services must all be prepared for disaster management (296). Disaster management often requires interfacing and coordinating with local, regional, state, and national agencies to end the disaster, provide rescue, and work toward recovery (297). On occasion, a coordinated international response is ideal especially when more than one nation participates in remote relief efforts after a disaster of humanitarian crisis (298). For healthcare facilities, preparation for an external disaster including earthquake, flood, or chemical/nuclear/biologic/radiologic/explosive exposures or injuries is just as important as preparing for an internal one such as a fire, active shooter event, or electrical system failure (299–301). Preparation typically leverages an all-hazards approach that supports response flexibility. With the rise in violent extremism, mass shootings, and weather-related disasters such as wildfires, hospitals and ICUs must prepare for patient surge at a single facility as well as load-balancing across local or regional facilities (302,303). If critical care must be delivered outside of the typical healthcare facility, quality care can be achieved—a lesson implemented during the recent SARS-CoV-2 pandemic (304,305). Preparation must also address the impact of the disaster and its management on how, when, and where public health measures are deployed (306). Public health measures have characterized emergencies besides COVID-19, including SARS, Middle East Respiratory Syndrome, H1N1, and Ebola, for example—all of which influenced ICU preparation and care (307,308). Data derived from such responses have helped articulate a set of potential core measures that help align the severity of patient illness or injury with required resources for a successful public health emergency response (309). Disaster competency should include initial burn injury care, especially as specialized burn centers may rapidly reach or exceed capacity during disaster care (310). As facilities became overwhelmed during COVID-19—and routine transfer pathways were no longer viable—telemedicine and telecritical care in particular helped provide resource sparing clinical expertise to help guide care at remote facilities bereft of critical care clinicians (311,312). Approximately half of all U.S. acute care hospitals are routinely without an intensivist on staff (313). COVID-19 patient care benefitted from the development and deployment of an electronic health record agnostic stand-alone telecritical care platform that linked bedside clinicians with remote intensivists in an on-demand fashion using nonnetwork-linked devices such as personal smartphones (314).

The generally resource replete civilian space differs from the more austere military reality. Regardless, the military success in both time-limited and prolonged austere field care bears important lessons for civilian disaster response (315–317). Military conflicts in spaces such as the Middle East introduced new injury patterns to those already well described in miliary medicine. Chief among those are injuries related to improvised explosive devices in open as well as enclosed spaces (318). Blast injuries including those of the lungs and brain complicate recovery and create disability whose impact exceeds patient recovery from primary injury such as penetrating trauma, burns, or limb loss (319,320). Mangled extremities from explosive injuries are so common that novel approaches to limb salvage are now common, including indwelling vascular shunts that are placed in a forward rescue location that remain in place during transport to a definitive care location. In-field mobile surgical teams bring critical care trained surgeons to the patient for damage control rescue (321). In contradistinction, civilian rescue requires bystander aid, emergency medical services transport, or, increasingly, Police transport (322).

The Boston Marathon domestic terrorism bomb attacks demonstrated the injury spectrum from IED detonation. It also underscored the benefit and necessity of bystander competency in immediate hemorrhage control—specifically tourniquet application—in conjunction with the value of “Good Samaritan” nontrauma facilities in saving life (323,324). Furthermore, the approach that was used—termed Staged Care—mirrors far-forward military aid with subsequent transitions to increasingly complex care facilities (Fig. 4). In military history, almost 90% of combat deaths occurred before the casualty reaches medical care. Advances in trauma care have dramatically reduced the combatant mortality rate. For example, 19% of wounded World War II soldiers died, and 15% of wounded Vietnam soldiers expired. Wounded soldier mortality in the recent Afghanistan conflict is less than 9% reflecting prehospital interventions, which bring critical care—and mobile surgical teams—into the field (321,325). One of those interventions is fresh whole blood as an aid in resuscitation that began in military medicine with the “walking blood bank” and has recently translated to civilian trauma care (47,326,327). Similar notions permeate naval operations to provide immediate rescue and complex care (328). Evacuation may include the now well-developed critical care air transport program that can successfully bring critically ill or injured patients—including those requiring ECMO—from anywhere in the world to a U.S. destination facility (329).

F4
Figure 4.:
This graphic demonstrates a civilian approach to disaster rescue leveraging local on-scene care, the use of nontrauma designated “Good Samaritan” facilities, as well as hospitals that are part of an existing network to transfer critically injured patients to a facility for definitive care. This integrated approach is termed “Staged Care.” Key support techniques that support survival are identified as well. EMS = emergency medical services.

Solid Organ Transplantation

Caring for patients with organ failure when now common aids such as dialysis, insulin, ventricular assist devices, or ECMO were not available fostered both collaboration and competition to develop successful approaches to transplantation. Solid organ transplantation became a reality in the 1950s, with the first successful kidney transplant at the Little Company of Mary Hospital in Chicago, Illinois by Richard Lawler; organ survival was only 53 days (330). The first long-term successful kidney transplant occurred at the Brigham and Women’s Hospital in 1954 with a transplant between identical twins; Joseph Murray received the 1990 Nobel Prize in Medicine for this landmark achievement (331). Pioneers in human transplantation also include James Hardy at the University of Mississippi (lung, 1963), Tom Starzl at the University of Colorado (liver, 1963), Richard Lillehei and Bill Kelly at the University of Minnesota (pancreas, 1966), and Christian Barnard of Capetown, South Africa, and Norman Shumway of Stanford (heart in 1967 and 1968, respectively) (332,333). Incremental progress relied on improved organ preservation, elucidating mechanisms of immune tolerance, routine human tissue typing, and the articulation of humoral immunity. Thereafter, effective immunosuppression became the overarching impediment to progress. Basic and clinical inquiry advanced immune suppression from azathioprine to cyclosporine and currently tacrolimus (334). Regimens that guide the use of induction agents (e.g., antithymocyte globulin, alemtuzumab, and basiliximab), antirejection prophylaxis (e.g., glucocorticoid and mycophenolate mofetil), and antiinfection prophylaxis (e.g., trimethoprim-sulfamethoxazole) further improved outcomes (335). Metabolic investigations flourished during transplantation’s early growth (336). For example, characterizing nonhepatic tissue oxygenation during transplantation laid the foundation for modern venovenous bypass intraoperative management (337,338). Combined surgical technique and medical therapy developed transplantation from an experimental field into that of standard of care for unrecoverable organ failure.

Currently, solid organ transplantation encompasses heart, lung, liver, kidney, pancreas, and multivisceral organ transplantation. Other transplants occur including cornea, small bowel, hand, abdominal wall, uterus, and face—advances that rely on the interface of medicine and technology including 3-D printing techniques (339–342). Adrenal and parathyroid transplantations including cellular transplantation are emerging techniques as well; cellular approaches offer the potential to vastly improve recipient numbers as it does not rely on a solid organ approach and may occur solely in a laboratory (343,344). Furthermore, partial organ transplantation approaches (liver, kidney, pancreas, single lung, and intestinal segment) have increased the number of recipients who benefit from transplantation, as well as allow living-related and living-unrelated organ donation to flourish. As transplantation has evolved, it has shaped team-based care in ICUs, immune suppression regimen development and refinement, infectious disease management, organ donation activities and policies, as well as the ethics surrounding different kinds of donation (345–347).

Successful organ transplantation on a national scale required the creation of organ procurement organizations (OPOs) and a national system of equitable organ allocation (e.g., the United Network for Organ Sharing). Organ donation links three overarching domains: organ donation, organ donor management, and donation ethics. Organ donation was previously limited to individuals declared brain dead most commonly after injury or cardiac arrest (348). However, changes in resuscitation influence the potential organ donor pool, especially those who undergo rescue using an extracorporeal technique that supports organ blood flow (349–351). The willingness to participate in organ donation appears to be asymmetric, with racial and ethnic minority groups less frequently participating in organ donation (352,353). This recognition offers a potential target for community and inhospital intervention to increase organ availability. Religious beliefs and a faith-based existence may substantially impact organ donation acceptability as well, helping drive the need for inhospital pastoral care services (354). As the number of potential organ recipients continued to climb, other approaches to increasing the potential donor pool or improving the outcome of donor management were needed (355). In particular, donation after cardiac death and organ donor management protocols increasingly characterize organ donation in adults and children (356–359). Investigations into potential donor screening or their management ahead of donation also helped allocate organs with a higher potential for viability and function into recipients (360–365). Newer avenues to further reduce variation in donor management include establishing donor management centers as stand-alone structures or in dedicated spaces within acute care facilities (366). The intensivist is integral to managing organ failure patients ahead of organ transplantation as well as donated organ transplant recipients in concert with the transplant team (367).

Ethical issues that surround organ donation are complex, are pervasive, and involve potential donors, potential recipients, families, clinicians, hospital administration, and OPOs alike (368). In particular, ethical and practical issues around donation after cardiac death—as opposed to donation after brain death—are more common (369–372). Brain death has been well established—at least in the United States—along specific criteria and pathways (373). Family members often embrace surrogacy with regard to decision-making for those who have not declared their desires with regard to organ donation, a challenging role that seems better borne when donation is viewed as beneficial even in the context of tragedy (374). These discussions often include how to approach end-of-life care (375,376). Transplant coordinators who work for the OPO, pastoral care, palliative care medicine, and, quite commonly, the bedside critical care nurse play key roles in hearing family concerns, understanding their values, preferences, as well as their understanding of the patient’s desires. Given the complexity of managing organ donors as well as transplant recipients, it is unsurprising that unique specialties have arisen to support post-transplantation management.

A surgical approach to organ failure thus spawned several new areas of specialty training and certification included histocompatibility, pediatric transplantation, transplant anesthesia, transplant pharmacy, transplant critical care fellowship programs, and transplant nurse coordination. Given the impact of immune suppression regimens on infection, sepsis, and septic shock, transplant infectious disease has emerged as a novel specialty (377,378). The need for such support arises from post-transplantation complications and their management including organ failure and sepsis (379–383). Unique therapies for rescue also aid in pretransplant management and better enable transplantation tolerance. A specific example is the molecular adsorbent recirculating system (MARS) for acute or acute-on-chronic liver failure (384). Those with acetaminophen induced hepatic failure may derived substantial benefit from MARS rescue and avoid requiring hepatic transplantation enhancing organ availability for others (385). Other technologic approaches have extended the recipient pool including direct cardiac transplantation for those on ECMO support, an approach that appears to have equal outcome compared with those who did not require ECMO (386). Although not a destination therapy, ECMO may serve as a bridge to transplantation. Since many of these therapies require anticoagulation, intraoperative and postoperative critical care management must address coagulopathy. It is in this aspect that the intensivist must be familiar with techniques such as thromboelastography that assess the integrity of the entire clotting cascade and allow one to discern component success from failure (387). Naturally, familiarity with thromboelastography spills over into other spaces such as traumatic brain injury in a complementary fashion (388). Therefore, the panoply of management techniques, diagnostic aids, and interventional therapeutics with which the intensivist must be conversant has rapidly expanded with regard to solid organ transplantation, some of which benefits patients with unrelated disease processes or injuries.

Foundations

Each of the above explored surgical science domains rests on foundations crafted by former surgeon-scientists. Table 1 celebrates those key leaders and their major achievements that have impacted critical care. As both the SCCM and Critical Care Medicine embark upon their next 50 years, it is fitting to recognize those whose discoveries have guided, enabled, or refined how modern care is deployed at the bedside for the critically ill or injured.

TABLE 1. - Key Deceased Surgeons and Foundational Work That Influenced Surgical Critical Care Medicine Inquiry, Discoveries, and Care
Surgeon Foundational Domain(s)
J. Wesley Alexander, MD Nutrition support after thermal injury to improve wound repair; surgical infections management (389)
William A. Altemeier, MD Hyperoxia driven injury during critical illness; founded multiple novel surgical research laboratories addressing infection, injury, and burns (390)
William Blakemore, MD Immune suppression related to surgery and its impact on outcome (391)
Frank B. Cerra, MD Multiple System Organ Failure pathophysiology; nutrition evaluation and support; pre-operative optimization to improve outcome (392–394)
Joseph M. Civetta, MD Therapeutic intervention scoring; Emergency General Surgery diagnostic evaluation; catheter related infection prevention; positive end-expiratory pressure optimization (395–397)
Louis R. Del Guercio, MD Blood Flow with cardiac massage; geriatric operative risk assessment; pleural space management during critical illness; founding member of the Society of Critical Care Medicine (398–400)
Stanley J. Dudrick, MD Developed Total Parenteral Nutrition (401)
Mitchell P. Fink, MD Developed sepsis definitions; ICU transfusion threshold benchmarks (402, 403)
Josef E. Fischer, MD Nutrition evaluation and support; enterocutaneous fistula management; lactate as a marker of perfusion; hair clipping to reduce surgical site infection (404–407)
Ake Grenvik, MD (dually trained in Surgery and Anesthesiology) Critical care medicine as a specialty; founding member of the Society of Critical Care Medicine (408–411)
John Howard, MD Led the U.S. Army Surgical Research Team (Korean War era) and initiated the repair of arterial injuries; physiologic response to injury; hemorrhagic shock resuscitation; founding member of the Society of Critical Care Medicine (412, 413)
John Ki`nney, MD Designed a unique research unit to care for and study acutely ill surgical patients; founding member of the Society of Critical Care Medicine (414)
John Kirklin, MD Developed the world’s first closed-loop surgical, computer-based ICU for post-cardiac surgery patients; founding member of the Society of Critical Care Medicine (415)
F. John Lewis, MD Credited with the first successful open-heart surgery; developed a computer-controlled system for continuous monitoring of ICU patients; founding member of the Society of Critical Care Medicine (416)
Steven F. Lowry, MD Systemic inflammation including molecular and cellular mechanisms; risk prediction in sepsis; surgical infection management (417–419)
Basil Pruitt, MD Burn injury care; injury prevention; avoiding excess resuscitation; inaugural editor of the Journal of Trauma (420–423)
Jonathan E. Rhoads, MD Developed Total Parenteral Nutrition; wound repair mechanisms and support approaches (401, 424)
Peter Safar, MD (dually trained in Surgery and Anesthesiology) Initiated the first physician-staffed general ICU in the United States; “father” of cardiopulmonary resuscitation and the ABCs of life support after cardiac arrest; developed the world’s first critical care medicine training program (University of Pittsburgh); founding member of the Society of Critical Care Medicine (425, 426)
William C. Shoemaker, MD Hyperdynamic cardiac performance in relation to outcome; oxygen debt; founding member of the Society of Critical Care Medicine; inaugural editor of Critical Care Medicine (427–429)
Douglas W. Wilmore, MD Helped develop total parenteral nutrition, and nutrition support after acute illness or injury; evaluated catecholamine levels after thermal injury as indicator of persistent inflammation and hypermetabolism (421, 430)
Robert F. Wilson, MD Intra-abdominal pressure impact on mucosal blood flow; coronary flow after adenosine infusion; founding member of the Society of Critical Care Medicine (431, 432)

CONCLUSIONS

The pursuit of new knowledge to improve the care of surgical patients impacts the care of patients of other specialties in ways that improve outcome and management. Tools and approaches including bedside ultrasonography, ECMO, surgical infection care, coagulopathy management, and shock resuscitation are common across ICUs of every specialty both adult and pediatric. Focused inquiry into inflammation, endotheliopathy, intestinal integrity, and microbiome alterations have fueled related discoveries that drive basic and translational research. Global events underscore the need for both man-made and natural disaster preparedness—events for which ICUs must specifically prepare regardless of patient population focus. Solid organ transplantation has crafted new approaches and new specialties that engage with patients with severe organ failure before, during, and after organ transplantation. Additionally, we are approaching the sought-after horizon of resuscitation for those with exsanguinating hemorrhage. What began as CPB with circulatory arrest has evolved into EPR that offers salvage for the current unsalvageable patient with critical injury. Finally, these discoveries and care evolutions have been shared in a global fashion within the pages of Critical Care Medicine over the last 50 years, serving as a guide to innovation, inquiry, and bedside care of the critically ill and injured.

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Keywords:

critical illness; disaster; infection; microbiome; resuscitation; transplantation; ultrasound

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