Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by Michigan University on 10/16/14 For personal use only.
Review
The management of severe community acquired pneumonia in the intensive care unit Expert Rev. Respir. Med. 8(3), 293–303 (2014)
Adamantia Liapikou*1, Edmundo RosalesMayor2 and Antoni Torres3 1 6th Respiratory Department, Sotiria Hospital, Mesogion 152, 11527, Athens, Greece 2 Department of Pneumology, Institut Clinic del To´rax, Hospital Clinic, Barcelona, Villarroel 170, 08036, Barcelona, Spain 3 Department of Pneumology, Institut Clinic del To´rax, Institut d’investigacions Biome`diques August Pi i Sunyer – IDIBAPS, -University of Barcelona – UB – Ciber de Enfermedades Respiratorias – CIBERES, Hospital Clinic, Barcelona, Villarroel 170, 08036, Barcelona, Spain *Author for correspondence: Tel.: +30 210 776 3458 [email protected]
informahealthcare.com
Severe CAP (SCAP), accounting for 6% of admissions to intensive care units (ICUs) needs early diagnosis and aggressive interventions at the most proximal point of disease presentation. The prognostic scores as the ATS/IDSA rule, the systolic blood pressure, multilobar infiltrates, albumin, respiratory rate, tachycardia, confusion, oxygen and pH or SCAP system are appropriate in early identification of eligible patients requiring admission to ICU. Then the recommended initial resuscitation in SCAP in the ICU consists of fluid volume intake titrated to specific goals after a fluid challenge and hemodynamic optimization. The first selection of antimicrobial therapy should be started in the first hour and would be broad enough to cover all likely pathogens. Combination therapy may be useful in patients with non refractory septic shock and severe sepsis pneumococcal bacteremia as well. After 6 hours the patient would be reevaluated in terms of hemodynamic stability and antibiotic and therapy. Future developments will focus on sepsis biomarkers, molecular diagnostic techniques and the development of novel therapeutic immunomodulaty agents. KEYWORDS: ICU • management • resuscitation • septic shock • severe community acquired pneumonia
Community-acquired pneumonia (CAP) is an important public health problem. When combined with influenza, it is currently the eighth leading cause of death in the USA and the most common infectious cause of death in the developed world. The term ‘severe CAP’ identifies a group of patients who have severe disease, who require intensive care unit (ICU) admission, who are prone to have complications and poor outcomes and who require a higher level of care [1,2]. The incidence of severe CAP (SCAP) increases in the last decade. Particularly, in a study of Woodhead et al. [3], they identified a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to a 24% rise in total ICU admissions (p < 0.001). However, in USA, a substantial reduction (54.8 per 100,000 [95% CI: 41.0–68.5]) in hospitalizations for pneumonia among adults after the introduction of 7-valent pneumococcal conjugate vaccine into the USA childhood immunization schedule in 2000 has been reported [4]. 10.1586/17476348.2014.896202
Direct admission to an ICU is usually required for patients who present with septic shock requiring vasopressors and/or acute respiratory failure requiring intubation and mechanical ventilation (MV). The mortality rate of patients who require admission to the ICU reaches 30–40% [1,2]. What’s more, incident cardiac complications are common in patients with CAP and are associated with increased short-term mortality. In a recent study from Canada including 1343 inpatients and 944 outpatients with CAP, incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). More than half of the events were diagnosed in the first 24 h and in patients with previously diagnosed coronary artery disease and SCAP [5]. Delayed ICU transfers may represent rapidly progressive pneumonia that was not obvious on admission [6]. Transfer to the ICU for delayed respiratory failure or delayed onset of
2014 Informa UK Ltd
ISSN 1747-6348
293
Review
Liapikou, Rosales-Mayor & Torres
Box 1. Definitions. • SIRS: Presence of two or more of the following criteria • Fever (core temperature >38˚C) or hypothermia (core
temperature 20 breaths/min or PaCO2 90 beats/min • WBC >12,000/mm3, 10% Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by Michigan University on 10/16/14 For personal use only.
• Sepsis: Patient meets the criteria for SIRS and has a
suspected or confirmed infection • Severe sepsis: Sepsis plus at least one organ dysfunction
– Sepsis-induced tissue hypoperfusion – Lactate above upper limits laboratory normal – Urine output 2 mg/dl (34.2 mmol/l) – Platelet count 1.5) • Septic shock: Sepsis plus persistent hypotension despite fluid
resuscitation, or hyperlactatemia PaO2/FIO2: Ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2); SIRS: Systemic inflammatory response syndrome; WBC: White blood cells. Data taken from [9].
septic shock is associated with increased mortality [7]. Hence, a major challenge in the management of CAP is to identify patients at risk for rapidly developing adverse medical outcomes among those presenting to the ED with no obvious reason for immediate ICU admission. In this review, we are referring to the management of SCAP, requiring admission to the ICU, because it requires intensive hemodynamic and antibiotic therapies. Definitions
SCAP is a progressive disease, and in the event of evolution from a local to a systemic infection the following spectrum of sepsisrelated complications may develop: sepsis, severe sepsis, septic shock and multiple-organ dysfunction (BOX 1) [8–10]. Its critical clinical deterioration can result from various processes: respiratory failure, circulatory failure, destabilization of preexisting comorbidity and appropriateness of initial antibiotic therapy. The inflammatory response starts with an infection that leads to a proinflammatory state with a complex interaction between anti-inflammatory and proinflammatory mediators, enhanced coagulation and impaired fibrinolysis. Severity of pneumonia
Because site of care is a major determinant of costs, a number of clinical prediction rules have been developed to identify patients with low mortality that can be safely treated as outpatients [11]. 294
The Pneumonia Severity Index and CURB-65 [12], are the most popular prediction rules but do not have sufficient operating characteristics to be useful for making ICU triage decisions in SCAP. In 2007, the IDSA/ATS issued guidelines [2] on the management of CAP include specific criteria to identify patients for ICU admission. This rule recommended that the presence of one of the major or three or more of the nine minor criteria would indicate ICU admission (BOX 2). The major criteria of the IDSA/ATS guidelines refer to patients with acute respiratory failure requiring invasive MV or septic shock. In a validation study, Liapikou and colleagues found that patients meeting the major criteria needed ICU admission, but those patients who had only minor criteria present had no increased mortality risk, regardless of how many criteria were met [13]. Although each of the two approaches has been proposed as a tool to guide the site of care decision, neither is ideal by itself, and both can be regarded only as providing decision support information that must be supplemented by clinical assessment and judgment. The new generation of clinical prediction rules focuses on the early detection of respiratory and circulatory failure. Systolic blood pressure, multilobar infiltrates, albumin, respiratory rate, tachycardia, confusion, oxygen and pH (SMART-COP) [14], Risk of Early Admission to ICU (REA-ICU) [15] and SCAP [16] scores seem to have operative characteristics similar to the ATS minor criteria but are less extensively validated. Espana and colleagues [16] derived the SCAP prediction rule that was shown to discriminate better than previous prediction rules between ED patients with and without CAP-related adverse medical outcomes, including 30-day mortality and ICU referral. The variables of the score were also grouped in six minor criteria (confusion, urea >30 mg/dl, respiratory rate >30/ min, multilobar bilateral infiltrates, PaO2
Review
The management of severe community acquired pneumonia in the intensive care unit Expert Rev. Respir. Med. 8(3), 293–303 (2014)
Adamantia Liapikou*1, Edmundo RosalesMayor2 and Antoni Torres3 1 6th Respiratory Department, Sotiria Hospital, Mesogion 152, 11527, Athens, Greece 2 Department of Pneumology, Institut Clinic del To´rax, Hospital Clinic, Barcelona, Villarroel 170, 08036, Barcelona, Spain 3 Department of Pneumology, Institut Clinic del To´rax, Institut d’investigacions Biome`diques August Pi i Sunyer – IDIBAPS, -University of Barcelona – UB – Ciber de Enfermedades Respiratorias – CIBERES, Hospital Clinic, Barcelona, Villarroel 170, 08036, Barcelona, Spain *Author for correspondence: Tel.: +30 210 776 3458 [email protected]
informahealthcare.com
Severe CAP (SCAP), accounting for 6% of admissions to intensive care units (ICUs) needs early diagnosis and aggressive interventions at the most proximal point of disease presentation. The prognostic scores as the ATS/IDSA rule, the systolic blood pressure, multilobar infiltrates, albumin, respiratory rate, tachycardia, confusion, oxygen and pH or SCAP system are appropriate in early identification of eligible patients requiring admission to ICU. Then the recommended initial resuscitation in SCAP in the ICU consists of fluid volume intake titrated to specific goals after a fluid challenge and hemodynamic optimization. The first selection of antimicrobial therapy should be started in the first hour and would be broad enough to cover all likely pathogens. Combination therapy may be useful in patients with non refractory septic shock and severe sepsis pneumococcal bacteremia as well. After 6 hours the patient would be reevaluated in terms of hemodynamic stability and antibiotic and therapy. Future developments will focus on sepsis biomarkers, molecular diagnostic techniques and the development of novel therapeutic immunomodulaty agents. KEYWORDS: ICU • management • resuscitation • septic shock • severe community acquired pneumonia
Community-acquired pneumonia (CAP) is an important public health problem. When combined with influenza, it is currently the eighth leading cause of death in the USA and the most common infectious cause of death in the developed world. The term ‘severe CAP’ identifies a group of patients who have severe disease, who require intensive care unit (ICU) admission, who are prone to have complications and poor outcomes and who require a higher level of care [1,2]. The incidence of severe CAP (SCAP) increases in the last decade. Particularly, in a study of Woodhead et al. [3], they identified a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to a 24% rise in total ICU admissions (p < 0.001). However, in USA, a substantial reduction (54.8 per 100,000 [95% CI: 41.0–68.5]) in hospitalizations for pneumonia among adults after the introduction of 7-valent pneumococcal conjugate vaccine into the USA childhood immunization schedule in 2000 has been reported [4]. 10.1586/17476348.2014.896202
Direct admission to an ICU is usually required for patients who present with septic shock requiring vasopressors and/or acute respiratory failure requiring intubation and mechanical ventilation (MV). The mortality rate of patients who require admission to the ICU reaches 30–40% [1,2]. What’s more, incident cardiac complications are common in patients with CAP and are associated with increased short-term mortality. In a recent study from Canada including 1343 inpatients and 944 outpatients with CAP, incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). More than half of the events were diagnosed in the first 24 h and in patients with previously diagnosed coronary artery disease and SCAP [5]. Delayed ICU transfers may represent rapidly progressive pneumonia that was not obvious on admission [6]. Transfer to the ICU for delayed respiratory failure or delayed onset of
2014 Informa UK Ltd
ISSN 1747-6348
293
Review
Liapikou, Rosales-Mayor & Torres
Box 1. Definitions. • SIRS: Presence of two or more of the following criteria • Fever (core temperature >38˚C) or hypothermia (core
temperature 20 breaths/min or PaCO2 90 beats/min • WBC >12,000/mm3, 10% Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by Michigan University on 10/16/14 For personal use only.
• Sepsis: Patient meets the criteria for SIRS and has a
suspected or confirmed infection • Severe sepsis: Sepsis plus at least one organ dysfunction
– Sepsis-induced tissue hypoperfusion – Lactate above upper limits laboratory normal – Urine output 2 mg/dl (34.2 mmol/l) – Platelet count 1.5) • Septic shock: Sepsis plus persistent hypotension despite fluid
resuscitation, or hyperlactatemia PaO2/FIO2: Ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2); SIRS: Systemic inflammatory response syndrome; WBC: White blood cells. Data taken from [9].
septic shock is associated with increased mortality [7]. Hence, a major challenge in the management of CAP is to identify patients at risk for rapidly developing adverse medical outcomes among those presenting to the ED with no obvious reason for immediate ICU admission. In this review, we are referring to the management of SCAP, requiring admission to the ICU, because it requires intensive hemodynamic and antibiotic therapies. Definitions
SCAP is a progressive disease, and in the event of evolution from a local to a systemic infection the following spectrum of sepsisrelated complications may develop: sepsis, severe sepsis, septic shock and multiple-organ dysfunction (BOX 1) [8–10]. Its critical clinical deterioration can result from various processes: respiratory failure, circulatory failure, destabilization of preexisting comorbidity and appropriateness of initial antibiotic therapy. The inflammatory response starts with an infection that leads to a proinflammatory state with a complex interaction between anti-inflammatory and proinflammatory mediators, enhanced coagulation and impaired fibrinolysis. Severity of pneumonia
Because site of care is a major determinant of costs, a number of clinical prediction rules have been developed to identify patients with low mortality that can be safely treated as outpatients [11]. 294
The Pneumonia Severity Index and CURB-65 [12], are the most popular prediction rules but do not have sufficient operating characteristics to be useful for making ICU triage decisions in SCAP. In 2007, the IDSA/ATS issued guidelines [2] on the management of CAP include specific criteria to identify patients for ICU admission. This rule recommended that the presence of one of the major or three or more of the nine minor criteria would indicate ICU admission (BOX 2). The major criteria of the IDSA/ATS guidelines refer to patients with acute respiratory failure requiring invasive MV or septic shock. In a validation study, Liapikou and colleagues found that patients meeting the major criteria needed ICU admission, but those patients who had only minor criteria present had no increased mortality risk, regardless of how many criteria were met [13]. Although each of the two approaches has been proposed as a tool to guide the site of care decision, neither is ideal by itself, and both can be regarded only as providing decision support information that must be supplemented by clinical assessment and judgment. The new generation of clinical prediction rules focuses on the early detection of respiratory and circulatory failure. Systolic blood pressure, multilobar infiltrates, albumin, respiratory rate, tachycardia, confusion, oxygen and pH (SMART-COP) [14], Risk of Early Admission to ICU (REA-ICU) [15] and SCAP [16] scores seem to have operative characteristics similar to the ATS minor criteria but are less extensively validated. Espana and colleagues [16] derived the SCAP prediction rule that was shown to discriminate better than previous prediction rules between ED patients with and without CAP-related adverse medical outcomes, including 30-day mortality and ICU referral. The variables of the score were also grouped in six minor criteria (confusion, urea >30 mg/dl, respiratory rate >30/ min, multilobar bilateral infiltrates, PaO2
