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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 3  |  Page : 117-142

Acute care for the three leading causes of mortality in lower-middle-income countries: A systematic review


1 Department of Critical Care Medicine, Einstein/Montefiore Medical Center, Bronx, NY, USA
2 Boston University School of Medicine, Boston, MA, USA
3 Department of Emergency Medicine, Boston Medical Center, Boston, MA, USA
4 Boston University School of Medicine; Department of Emergency Medicine, Boston Medical Center, Boston, MA, USA

Date of Web Publication27-Aug-2018

Correspondence Address:
Dr. Gabrielle A Jacquet
Boston Medical Center, One Boston Medical Center Place, Dowling 1 South Emergency, Boston, MA 02118
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJCIIS.IJCIIS_22_18

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   Abstract 


According to the World Health Organization, the three leading causes of mortality in lower-middle-income countries (LMIC) are ischemic heart disease (IHD), stroke, and lower respiratory infections (LRIs), causing 111.8, 68.8, and 51.5 annual deaths per 100,000, respectively. Due to barriers to healthcare, patients frequently present in critical stages of these diseases. Measured implementations in critical care in LMIC have been published; however, the literature has not been formally reviewed. We performed a systematic review of the literature indexed in PubMed as of October 2017. Abstracts were limited to human studies in English, French, and Spanish, conducted in LMIC, and containing quantitative data on acute care of IHD, stroke, and LRI. The search resulted in 4994 unique abstracts. Through multiple rounds of screening using criteria determined a priori, 161 manuscripts were identified: 38 for IHD, 20 for stroke, 26 for adult LRI, and 78 for pediatric LRI. These studies, predominantly from Asia, demonstrate successful diagnostic and treatment measures used in providing acute care for patients in LMIC. Given that, only four manuscripts originated in Central or South America, original research from these areas is lacking. IHD, stroke, and LRIs are significant causes of mortality, especially in LMIC. Diagnostic and therapeutic interventions for IHD (monitoring, medications, thrombolytics, percutaneous intervention, coronary artery bypass graft), stroke (therapeutic hypothermia, medications, and thrombolytics), and LRI (oxygen saturation measurement, diagnostic ultrasound, administration of oxygen, appropriate antibiotics, and other medications) have been studied in LMIC and published.

Keywords: Acute care, critical care, ischemic heart disease, lower-middle-income countries, lower respiratory infection, stroke


How to cite this article:
Dahn CM, Wijesekera O, Garcia GE, Karasek K, Jacquet GA. Acute care for the three leading causes of mortality in lower-middle-income countries: A systematic review. Int J Crit Illn Inj Sci 2018;8:117-42

How to cite this URL:
Dahn CM, Wijesekera O, Garcia GE, Karasek K, Jacquet GA. Acute care for the three leading causes of mortality in lower-middle-income countries: A systematic review. Int J Crit Illn Inj Sci [serial online] 2018 [cited 2018 Nov 15];8:117-42. Available from: http://www.ijciis.org/text.asp?2018/8/3/117/239894




   Introduction Top


According to the World Health Organization (WHO), the three leading causes of mortality in lower-middle-income countries (LMIC) are ischemic heart disease (IHD), stroke, and lower respiratory infections (LRIs), causing 111.8, 68.8, and 51.5 annual deaths per 100,000, respectively.[1] The 2010 Global Burden of Disease (GBD) Study indicated that IHD is the leading cause of mortality and loss of disability-adjusted life years (DALYs) worldwide, accounting for roughly seven million deaths and 129 million DALYs annually.[2],[3] Noncommunicable disease processes have been a leading cause of death in high-income countries for decades. However, the previous focus in LMICs has been on communicable diseases and now there is an aging population thought to account for a shift to noncommunicable disease deaths. For example, there have been great improvements in the age-adjusted mortality rates associated with IHD over the past two decades; however, rates in high-income countries are largely accountable for this improvement and rates in the LMIC remain largely unchanged.[4] There have been efforts to decrease mortality in LMIC including communicable and noncommunicable diseases, but they have been primarily focused on preventative methods (clean water, environmental safety measures, safe sexual practices, and prenatal care).[5],[6] Some research suggests that this mortality can be decreased with effective, focused, and evidence-based acute care. Seven out of the top 15 causes of morbidity and mortality worldwide can be reduced through the provision of high-quality, cost-effective emergency care.[7] Delving further, on account of the epidemiologic transition and concurrent decreased access to health care, patients often present in later-stage forms of illness and require more acute interventions. As a result, there must be a greater emphasis on acute care for noncommunicable diseases. A recent systematic review identified quantitative data on the delivery of emergency care in LMICs.[8] Our literature review aims to present updated specific quantitative data for the acute care of the 2015 three leading causes of death in LMIC.


   Methods Top


Systematic search and selection criteria

We performed a systematic review of the literature indexed in PubMed as of October 2017. Abstracts were limited to human studies in English, French, and Spanish. We used a comprehensive list of terms [Appendix A], including “Critical Care,” “Critical Illness,” “Emergency Medicine,” “Acute Disease,” “Ischemic Heart Disease,” “Cerebrovascular Disorders,” “Lower Respiratory Tract Infections,” and other similar terms along with individual names of LMICs according to the World Bank.[9] The initial search returned 5349 titles; 355 were duplicates that were excluded before review. On primary review of the remaining 4994 abstracts, 4265 were excluded by two reviewers (with conflicts resolved by a third) using the following a priori exclusion criteria: Not human; not in English/French/Spanish; not in LMIC; not a complete manuscript (e.g., only an abstract, poster presentation, lecture, letter, or short communication); not conducted in a LMIC – as defined by the World Bank classification of countries as of October 27, 2015, as the search was initially done in November 2015 and then updated in October 2017; and a manuscript without a focus on the acute care of IHD, stroke, or LRI. The abstracts of the remaining 729 manuscripts were screened by two reviewers (with conflicts resolved by a third); 127 were excluded based on inability to retrieve the manuscript. The remaining 602 manuscripts were reviewed by two reviewers, with conflicts resolved by a third, for the following inclusion criteria: manuscripts with a primary focus on or detailed section including specific acute care interventions for IHD, stroke, and LRI. Data were then extracted from the 161 manuscripts identified. All screening and data extraction were completed using Microsoft Excel. The study institution did not require the Institutional review board approval, as this was a review limited to the existing literature.




   Results Top


The search produced 5349 titles of interest, of which 161 manuscripts were selected for full-text analysis in this review: 38 IHD, 20 stroke, 26 adult LRI, and 77 pediatric LRI [Figure 1].
Figure 1: Flowchart of the systematic review process (PRISMA diagram)

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Ischemic heart disease

Within the IHD subgroup, articles were primarily from Asia (19), the Middle East (9), and Eastern Europe (8), with only one from Africa and one from South America. Articles focused on outcomes after cardiopulmonary resuscitation, medications, thrombolytics, percutaneous coronary intervention, coronary artery bypass graft (CABG), intra-aortic balloon pump (IABP), and other interventions [Table 1].
Table 1: Acute coronary syndrome articles included

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Diagnosis

Acute coronary syndrome (ACS) carries the risk of mortality in the acute setting, and survivors carry the risk of recurrent ACS or developing chronic heart failure and reduced exercise tolerance, representing significant DALYs. Diagnosis of ACS requires an electrocardiogram (EKG) machine and the expertize to interpret the symptoms of the patient and the EKG and to know the indication and contraindications of various therapeutic agents. Diagnosis and treatment for ACS do not require laboratory capacity for cardiac enzymes but if used, troponin is the preferred biomarker for cardiac injury, and point of care testing can be used in rural settings.[10] Compared with high-income countries, the age distribution of patients presenting in ACS is younger, with 50% of patients from one case series in Pakistan younger than 55 years of age.[11] Men represent the majority of patients presenting with ACS across many sites.[12],[13],[14],[15],[16] Although men may have a higher incidence of ACS and coronary artery disease risk factors, men may also be more likely to present to care. A review of patients presenting to over 100 hospitals in India found equivalent medical therapy and mortality between men and women.[17]

Early recognition seems to be key to providing a mortality benefit. A study in Brazil in a tiered healthcare setting found an average delay of 28 min from provider to EKG obtainment and another average 153 min for the percutaneous intervention (PCI) center to review the EKG and get the patient transferred.[18] In India, an electronic Intensive Care Unit (eICU) was established whereby EKGs were obtained and transmitted and interpreted by remote cardiologists, who made treatment recommendations resulting in the mean door to needle time of 30 min versus 180 min before eICU with a reduction of >70% in mortality.[19] Although IHD patients can be managed in a general medical ward, a specific cardiac unit may give evidence-based treatments more consistently and promptly.[20],[21] In addition, units with cardiac monitors can detect arrhythmias or arrests more quickly with better outcomes.[22] On the contrary, thrombolytic use in the pre-hospital setting as well as improving PCI availability using tertiary center hospitals without access to cardiothoracic surgeons have both shown decreased mortality secondary to earlier diagnosis and intervention.[23],[24]

Treatment

Evidence-based treatment of IHD can be applied in a stepwise manner, depending on the capacity of the facility and the financial resources of the patient and the payment model of the health care system. The first level of treatment is medical management. Medical management of ACS with propranolol was shown to improve the left ventricular ejection fraction (LVEF) and functional outcomes in India.[25]

The next level of treatment is systemic thrombolysis with streptokinase or tissue plasminogen activator (TPA); these medications can reduce mortality in LMIC.[24],[26],[27] Interventional approaches such as PCI with balloon angioplasty or stenting require greater infrastructure and more advanced practitioners. PCI was shown to have better outcomes than thrombolysis.[13] Compared with high-income countries, PCI tends to be used in more acute situations rather than electively, but it can have comparable outcomes. Mortality is much higher in patients who present in cardiogenic shock, and time to patient presentation and outcomes vary by site.[12] Using the transradial approach reduces hemorrhagic complications.[23] When PCI does not successfully reopen the stenosed vessel, termed slow flow, patients have higher 30-day mortality.[28] Abciximab administered intravenously has been used to treat slow flow states.[29]

Finally, CABG can be used as an acute therapy for ACS. Even within a month, CABG improved LVEF following ACS.[30] Despite the more invasive nature of CABG compared to PCI, CABG can have better outcomes and better cost-effectiveness than PCI in LMIC.[31] Performing CABG off-pump reduces costs but has similar outcomes for low-risk patients with left main coronary artery disease.[32] Some centers use CABG as the first-line therapy for critical left main stenosis and use PCI as a back-up for patients too critically ill to undergo surgery.[33]

Patients in cardiogenic shock can be supported with inotropes, however, overall mortality is high, whether treated with PCI[12],[34] or CABG.[35] Furthermore, for patients who present in cardiac arrest, survival to hospital discharge is around 5%.[36]

The range of treatment options for ACS is not mutually exclusive. Thrombolysis can be administered during preparation for PCI,[34] with similar outcomes with primary PCI and thrombolysis followed by PCI.[37] In addition, PCI can treat occluded grafts that cause cardiac arrest following CABG.[38] Furthermore, if the multi-vessel disease is diagnosed during PCI, CABG can be available as a further treatment option.[39]

Other interventions that have been performed for patients with limited options included IABP for patients with refractory angina or cardiogenic shock.[40],[41] Cardiac shock wave therapy (CSWT) application to the ischemic myocardium in patients with refractory angina pectoris was found to improve symptoms and reduce the severity of ischemic areas at 6 months after CSWT treatment compared with the baseline.[42]

Stroke

Within the stroke subgroup, articles were primarily from Asia (10), followed by Africa (5), Middle East (3), and Eastern Europe (2). Articles focused on diagnostic methods, body temperature, medications, thrombolytics, endovascular treatments, and system changes [Table 2].
Table 2: Stroke articles included

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Diagnosis

Clinical scoring systems to differentiate hemorrhagic versus ischemic stroke were found to be too unreliable to guide treatment decisions.[43] Patients who present promptly with an ischemic stroke will have normal nonenhanced computed tomography (CT) scans. For those patients, CT perfusion (CTP), can be used to identify which patients have perfusion defects that might respond to thrombolysis, identifying two candidates out of 42 patients presenting with stroke.[44] Accurately estimating stroke burden can be difficult, as a Ukranian town prospective following of stroke patients found a burden above local statistics from death certificates but below WHO estimates. Thirty-day case fatality was 23.3%, including patients that died prior to reaching the hospital.[45]

Hemorrhagic stroke can occur with acute hypertension and chronic hypertension is a risk factor. For patients who survive the initial bleed, complications include rebleeding and well as vasospasm. Vasospasm peaks in the 5–14 day period following the initial bleed.[46]

Thrombolysis

A retrospective study of patients presenting to the emergency department with symptoms of acute stroke found that most present outside the window of treatment with thrombolysis. The nine patients who received TPA had similar mortality and functional outcomes as those who did not receive TPA, although the study was limited by small numbers and retrospective design.[47] A retrospective look at two tertiary care centers in Pakistan found TPA used in 18/1185 (1.5%) stroke patient at one hospital and 3/575 (0.52%) patients at another hospital. Of the 21 patients who received the TPA, 7 (33%) were not eligible according to protocol, largely because of ischemic changes visible on head CT. Four of those patients had hemorrhage and three died.[48] A review of 62 consecutive stroke patients presenting to a tertiary care hospital in India identified late presentations of patient, availability of CT, and the high cost of TPA as the major barriers to thrombolysis. Of the 62 patients, 7 presented within 3 h of stroke onset, had no contraindications to TPA, but did not receive TPA as the confirmatory CT did not happen until the patient was outside of the window.[49]

Endovascular interventions

The use of endovascular techniques in subarachnoid hemorrhage resulted in 85% of patients without significant disability, and <2% had a procedure related fatality.[46] Although no control group was used, this case series demonstrates good results from endovascular techniques. There were no primary studies found meeting the study criteria discussing endovascular techniques like thrombectomy in LMIC.

Other interventions

Patients with fever had mortality rates of 51.78% in those with hemorrhagic stroke and 56.66% in those with ischemic stroke, compared with 13.5% and 8.8% in normothermic groups, respectively.[50] No data were presented on whether therapeutic interventions to reduce hyperthermia affect mortality. Controlling blood pressure after a hemorrhagic stroke prevents extension of the bleed. A nonrandomized trial of atenolol versus other antihypertensives found 11.4% mortality in the atenolol group compared with 37.3% in the nonatenolol group.[51] In 1995, Dalal and Dalal found that nimodipine started early after diagnosis of an ischemic stroke resulted in reduced disability, although no impact on mortality: 77.6% compared with 58.1% in the control group showed improved functional status.[52] Introducing a dedicated stroke ward reduced mortality from 8.9% to 2.1%, with an associated decrease in pneumonia, hemorrhage, and pressure sores while also reducing the average length of stay.[53] Presence of factors such as low Glasgow Coma Scale (GCS) or clinical progression is associated with the need for mechanical ventilation.[26] A nonrandom comparison of heparin plus elastic stockings compared with elastic stockings alone for deep vein thrombosis (DVT) prevention found only one DVT in the stocking group. A total of 12% of patients in the heparin group died compared with 20% in the control group, suggesting that heparin is safe for DVT prophylaxis in patients with acute intracerebral hemorrhage.[54]

In 1978, Gupta et al. randomized patient to steroids or placebo and found improved survival in patients with hemorrhage receiving steroids, but overall, no significant difference was found with steroids.[55] Over two decades later in 2001, Ogun used much higher doses of steroid and had higher overall mortality, but found no difference in mortality compared with placebo.[56] Other treatments under investigation include transcranial magnetic stimulation to improve motor function following stroke.[57]

Lower respiratory infection

Within the LRI adult subgroup, articles were primarily from Asia (9) and Eastern Europe (6), followed by Africa (5), the Middle East (4), and multiple regions (3) [Table 3].
Table 3: Lower respiratory infections adult articles included

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Within the LRI pediatric subgroup, articles were primarily from Asia (30), followed by Africa (22) and the Middle East (7), Eastern Europe (4), and multiple regions (8), with very few from Oceania (2), South America (2), and Central America (1) [Table 4].
Table 4: Lower respiratory infections pediatric articles inlucded

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Level of care

Acute LRIs present with a range of severity in part depending on comorbidities. Various severity scores and risk factors are associated with mortality including CURB65 and CRB65[58] as well as Acute Physiology and Chronic Health Evaluation II (APACHE II).[59] A low-risk subsection of patients can be treated at home,[58] whereas others require hospitalization and even intensive care. Patients treated in intensive care or admitted with severe pneumonia have mortality ranging from 20% to 50% depending on the report.[60],[61],[62] The strategies to reduce mortality include respiratory support, antibiotics, and adjuvant therapies.

Noninvasive ventilation

Patients with acute lower respiratory tract infection may require some degree of respiratory support, in a continuum from supplemental oxygen, to noninvasive mechanical ventilation, to intubation. Each of these supports can be offered even if more advanced supports are not available as backup.

Oxygen is listed as an essential medicine by the WHO[63] but is not readily available in many places. A total of 231 facilities in 12 African countries were surveyed, and 43.8% reported always having access to a source of oxygen, whether cylinder or concentrator. Oxygen concentrators require a dependable electricity supply but are cheaper than oxygen cylinders and do not require replacement.[64]

The Philippines established a national program for control of acute respiratory infection, and with donor support were able to roll out training and medications and supplies such as oxygen throughout the country. Without on-going donor support, however, the supply lines were unable to be maintained, and the measurement and evaluation were insufficient to measure the quality of the intervention.[65] Noninvasive ventilation (NIV) is associated with reduced mortality, although no randomized controlled trials exist.[59],[60],[61] A total of 40 patients admitted to the ICU with acute hypoxemic respiratory failure but not immediately intubated were trailed on NIV, and 47.6% of those patients subsequently required intubation. For a group largely composed of acute respiratory distress syndrome patients, NIV had a high failure rate. The worse the blood gas initially, the higher the risk of subsequent intubation. The authors conclude that although NIV had good outcomes with chronic obstructive pulmonary disease (COPD) and cardiogenic pulmonary edema, patients have to be carefully selected if they have other etiology of respiratory failure.[66] In Turkey, the following risk factors of late failure of noninvasive mechanical ventilation were found: high APACHE II score, high CRP level, low GCS, low albumin, weak cough, bad compliance to noninvasive mechanical ventilation, the presence of bronchiectasis/peptide nucleic acid, and absence of improvement of PaO2/FiO2.[67]

Empiric antibiotic choice

International and local treatment guidelines guide choice of empiric antibiotics, as patterns of etiologic agent and sensitivities varies by location. Identifying a specific bacterial etiology for pneumonia via blood cultures, sputum cultures, or even lung aspiration presents delay, low yield, and high cost.[68] Despite blood cultures on every patient and many patients having bronchoalveolar lavage cultures, only 25% of patients had a specific infectious pathogen identified. Given this low yield and the delayed results of cultures, treatment has to be started empirically and should reflect the local epidemiology.[62] To guide the choice of empiric antibiotics, we need to understand the local burden of various infections and the patterns of drug effectiveness. For instance, in Southeast Asia, sputum cultures of patients with acute COPD exacerbations showed a range of pathogen, including Pseudomonas, depending on the country. Overall, fluoroquinolones showed high susceptibilities and are a good empiric choice.[69]

Drug effectiveness is different than drug sensitivity, as some strains with in vitro resistance show clinical response.[70] A total of 300 patients with COPD exacerbation were treated with cefaclor or clarithromycin with similar efficacy. COPD exacerbations are not always bacterial, but antibiotics can produce clinical improvement.[71] Lebanon has published national treatment guidelines depending on the level of severity.[72]

In Tanzania, patients meeting the IMAI criteria for severe pneumonia had investigations that diagnosed etiology in 37% of patients, and among all patients, empiric ceftriaxone had the highest utility, working against known etiology in 17% of patients. Other diseases (cryptococcosis, histoplasmosis, Q fever, Rickettsial diseases) were common and need their specific treatment.[73] A cohort of patients with CAP in France were significantly older with more comorbidities than in Conakry, while those in Conakry were more likely to have initial shock and herpes. Mortality (6% vs. 8%) and clinical recovery (88% vs. 85%) were similar in both settings despite penicillin along being used in the majority of cases in Conakry and multiple or second-line antibiotics being often used in France.[74]

Of 202 isolates of Klebsiella pneumonia, 77.7% produces ESBL. While the study included the majority of urinary specimens, the findings held true for respiratory specimens. Based on individual sensitivity testing, the most widely efficacious antibiotic was imipenem.[75]

A total of 45 patients with lung abscesses were treated over 3 years. Twenty-nine were treated medically and 5 died. Sixteen were treated surgically and six died. Chest radiograph showed air-fluid levels. Sputum culture grew out a single organism in 11 patients. Massive hemoptysis was the primary indication for surgical intervention.[76]

Viral respiratory infections

Viral infections can present with critical illness benefiting from advanced interventions. Sixty-one patients were admitted to ICU in Turkey with H1N1. Mortality was 50.8% overall. Many patients had hypoxemic respiratory failure. Use of noninvasive motion ventilator was associated with increased survival.[59] For patients with influenza, investigators found increased mechanical ventilation requirement in female with pregnancy, diabetes mellitus, hypertension, tachypnea, bilateral lung involvement or involvement of RU/middle/multiple zones, or cardiac involvement.[77]

Other treatments

In addition to antibiotics and respiratory support, adjunctive treatment raises the possibility of improved outcomes. ADAPT-232 a mix of plant extracts speeds the recovery from pneumonia and increases the quality of life during convalescence in a placebo-controlled trial.[78] A meta-analysis of five studies of Vitamin A in acute lower respiratory tract infections showed no difference in recovery or mortality.[79]


   Discussion Top


As noted in the GBD and the WHO literature and reiterated in our review, the burden of critical care illness predominantly affects LMIC, with up 50%–70% of total deaths from conditions that could benefit from the availability of critical care versus <20% in high- and upper-middle-income settings.[80] While intuitively it is often argued that critical care is not practical in low-resource settings, critical illness in ubiquitous and acute care goes beyond ventilators and inotropes. Critical care provision can be simplified into three main components: timely identification of the critically ill, access to and delivery of resources to the acutely ill and definitive management and recovery from illness.[81] This literature review focuses on the three leading causes of death and evidence surrounding acute care in LMICs and demonstrates repeatedly the feasibility in providing acute care in this context.

Timely recognition of illness is of utmost importance to acute care. This is something that must happen outside of intensive care settings likely ICUs and emergency departments as well, including in operating rooms and medical wards, and in the community. Many of the studies noted above focus on timely recognition. For example, in the case of IHD, EKG availability is one limitation while the interpretation of the EKG is another. Some creative solutions, like the one using telemedicine methods in India[19] can make a limited resource, such as a specialist, more feasible. Regarding stroke care, recognition was difficult as well showing that low resource stroke scores and clinical signs were unable to identify hemorrhagic versus ischemic strokes. Other methods if CT scan was unavailable like biomarkers were discussed, but further research would be needed to implement any potentially meaningful change. When CT scan was available there was also discussion of using CTP in addition to better identify patients who might receive thrombolysis when the timing of onset was unknown, but further research is needed here as well. Similarly, many studies were devoted to early recognition of LRIs as well as classification of severity of illness to better triage patients on the need for antibiotics, fluid administration, and a higher level of care (home vs. ward vs. ICU). Multiple studies showed clinical symptoms that can be used to make a diagnosis and severity including the WHO guidelines for pneumonia. Other studies indicated oxygen saturation when available was more useful to diagnose and prognosticate, and the majority of studies indicated that chest X-ray (a limited resource in many settings) was not necessary or useful in identifying or treating a patient. Similarly, with LRI being so rampant and health-care delivery being limited, many studies looked at whether community health workers or volunteers could be properly trained to recognize LRI and know when to give antibiotics or transfer to a higher level of care and overall showed favorable outcomes.

Access and delivery of care are arguably the most relevant in terms of acute care delivery in LMIC. Things such as transportation to a hospital, available resources at any given care facility, and the amount of personnel, medication, ventilators, ICU beds, etcetera for acute care provision is minimal but also variable across different systems. For example, of 36 low-income studies included in a systematic review in 2015, <50% had any publishable data on ICU resource availability, and of the countries that did have publishable data, the ICU bed per million persons ranged from 1.0 to 16.7.[82] Whenever a treatment or resource is limited, it is important to decide which patients will have the most benefit and certainly avoid it in patients for whom it may cause harm. Outcomes of PCI for example were less favorable when a patient was in cardiogenic shock, possibly highlighting an area for less resource intensive care when there is limited availability. Similarly, the literature above noted that there seemed to be improved functional outcomes for patients with stroke who were in a care-specific stroke ward, but no scoring systems were found to identify which patients might be of most benefit.

Definitive management of a patient and the evidence supporting the treatment varies depending on the context, whether related to the difference in time to care, inherent to the disease processes, epidemiology or other differences. A great example of this is the Fluid Expansion as Supportive Therapy trial in which fluid boluses for septic children in Africa increased mortality, contrary to the evidence of sepsis management to date in developing countries.[83] The best management supported by evidence for acute care in LMICs is largely unknown and this review is the first look at three specific diseases and what is known to date.

Regarding IHD, the literature above repeatedly across different LMIC, finds thrombolytic use and PCI to have favorable outcomes and to be feasible when available but it is limited due to cost, personnel, and delays in recognition of disease as noted. Both medical treatment and thrombolysis require a supply chain for the medications but do not require additional infrastructure. Patients with PCI have good outcomes, and even when performed in a place without cardiothoracic surgery availability, outcomes were favorable. There were minimal reports on CABG or IABP, something done commonly in developed countries, secondary to the lack of resources and availability.

For ischemic CVA, systemic thrombolysis, accepted as a standardized treatment in high- and high-middle-income countries, seems to have increased mortality in studies done in LMIC but more research needs to be done to determine if this is related to diagnosis and timing, poor quality studies or something inherently different in the disease process or care. Less resource intensive and less costly treatments such as atenolol and nimodipine show favorable outcomes for stroke patients as well as subcutaneous heparin for venous thrombosis prophylaxis in intracranial hemorrhage patients. Endovascular techniques to address CVA (outside of subarachnoid hemorrhage) that are more resource intensive but have had hugely positive results in high-resource countries are unstudied in LMICs to date.

In cases of LRI, oxygen therapy is a mainstay of treatment but often unavailable, not to mention noninvasive and invasive ventilation machines. Oxygen therapy did not seem to make a difference in patients with mild disease, NIV was more useful for patients with COPD and CHF components to their disease process and for children rather than adults and actually had an increase in mortality for some adult patients with pneumonia and delayed invasive ventilation. When unavailable, the treatment remains limited to antibiotics, and when required source control from empyema drainage as the mainstays of treatment. There are many studies discussing the different antibiotic resistance patterns and recommended antibiotics depending on epidemiologic or outcome data of patients in different areas as well as different prevalence rates and risk factors for unrecognized HIV, tuberculosis, measles,  Salmonella More Details, and other atypical pathogens. There are also many studies showing the feasibility of training to avoid the unnecessary antibiotic use and when to give empiric antibiotics. However, research does not exist for all regions, and the correct choice makes a difference between life and death for many people as well as having potential benefit in decreasing overall multidrug-resistant organisms. Many other definitive management choices that remain understudied or unstudied for acute care of IHD, CVA, and LRI in LMICs may have significant effects on morbidity and mortality.

Limitations of this review include the inherent bias from primary studies included in a systematic review. To minimize bias, the methodology of a clear and consistent research question, strict inclusion and exclusion criteria, and three reviewers was used; however, potential bias may be introduced by the exclusion of studies not published in English, French, or Spanish. Furthermore, the majority of studies were from Asia and generalizability may be limited, particularly to Central and South America. In addition to highlight implementable and effective examples, we only included studies with measured quantitative outcomes; as a result, discussion articles and review pieces without quantitative data were excluded. Finally, with any systematic review, there is the inevitable possibility of “missing” an article however we made a great effort to avoid this by using duplicate screening with multiple reviewers. The purpose of this study was for an expansive review of available literature on the topic, but further study improvement may include a qualitative review of the studies included and a sensitivity analysis to see if any conclusions on best practices might be drawn.


   Conclusions Top


Acute care of patients with IHD, stroke, and LRI in low-and middle-income countries has been studied. There are many studies demonstrating feasibility and benefit of acute care interventions in these settings including but not limited to percutaneous coronary intervention, stroke-specific ward care, and improved mortality and decreased morbidity in particular patients with oxygen therapy or NIV with LRI. Understanding acute care in these settings is a growing field of interest with increasing recognition of decreased morbidity and mortality as well as increased cost-effectiveness. Further research of critical care interventions in underrepresented LMICs in paramount.

Acknowledgments

We would like to thank Kathleen Shea for obtaining manuscripts and Alissa Link for constructing and conducting the initial references search.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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