[Severe metabolic disorder associated with an enterovesical fistula. Report of one case]. / Trastorno grave del medio interno por fístula enterovesical, a propósito de un caso clínico.

Enterovesical fistula (EVF) is a fistulous communication between the intestine and the bladder. It is uncommon and its classic clinical manifestations are the presence of pneumaturia, fecaluria, suprapubic pain and recurrent urinary infections. Surgical repair of EVF leads to rapid correction of both diarrhea and metabolic abnormalities. We report a 73-year-old diabetic woman with a neurogenic bladder secondary to a spine meningioma. She presented with diarrhea, vomiting, impaired consciousness and metabolic acidosis. She developed hypernatremia, hypokalemia, hypocalcemia, and hypophosphatemia, which were successfully corrected.

[Risk factors for adverse drug reactions in patients admitted to intensive care units]. / Determinación de factores de riesgo a reacciones adversas a medicamentos mediante farmacovigilancia intensiva en UCI.

BACKGROUND: Patients hospitalized in intensive care units (ICU) are at higher risk of having adverse drug reactions (ADR). AIM: To determine risk factors for ADR, through intensive pharmacological surveillance at the ICU. PATIENTS AND METHODS: An observational, descriptive and prospective study was made, determining risk parameters in patients who experienced ADR. RESULTS: Eighty-five patients were surveilled and 24 (28%) had an ADR. A total of 48 drugs responsible for at least one ADR were identified. Seventy-three percent ADR were moderate and 27% were severe. The clinical variables significantly associated with ADR were a history of allergies, a high body mass index, the reason for admission, an APACHE II score ≥ 14 points, the use of invasive mechanical ventilation and more than seven days of hospitalization. The pharmacological variables associated with ADR were polypharmacy and medication associations and combinations. CONCLUSIONS: The identified risk factors have a great impact on pharmacokinetic and pharmacodynamic parameters, and should be considered to avoid the appearance of ADR.

[Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital]. / Neurología hospitalaria y COVID-19: serie de 96 pacientes evaluados en un hospital universitario.

BACKGROUND: There are multisystemic consequences secondary to SARS- CoV-2 infection. AIM: To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. METHODS: Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. RESULTS: Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. CONCLUSIONS: The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

[Expanding ICU facilities in a pandemic scenario]. / La criticidad de las Unidades de Intensivo. Ampliando las Unidades en tiempos de pandemia.

Our country is suffering the effects of the ongoing pandemic of coronavirus disease (COVID-19). Because the vulnerability of healthcare systems, especially the intensive care areas they can rapidly be overloaded. That challenge the ICUs simultaneously on multiple fronts making urgent to increase the number of beds, without lowering the standards of care. The purpose of this article is to discuss some aspects of the national situation and to provide recommendations on the organizational management of intensive care units such as isolation protocols, surge in ICU bed capacity, ensure adequate supplies, protect and train healthcare workers maintaining quality clinical management.

Effect of Lactamase Inhibitors on the Biosensor Penp during the Measurement of Lactam Antibiotics Concentration.

PenP is a fluorescent biosensor of lactam antibiotics (LA). It is structurally derived from the mutant lactamase TEM-1 comprising the substitution E166C, where fluorescein is covalently linked to cysteine. The presence of LA in the medium produces a change in the intrinsic fluorescence level of the biosensor, and the integral of the fluorescence level over time correlates directly with the LA concentration. Previously, we have successfully used PenP to determine the concentration of lactam antibiotics in clinical samples. The use of lactamase inhibitors (LI) is a common strategy to enhance the effect of LA due to the inhibition of an important resistance mechanism of pathogenic microorganisms. Structurally, LI and LA share the common element of recognition of lactamases (the lactam ring), but they differ in the reversibility of the mechanism of interaction with said enzyme. Because the biological recognition domain of PenP is derived from a lactamase, LI is expected to interfere with the PenP detection capabilities. Surprisingly, this work provides evidence that the effect of LI is marginal in the determination of LA concentration mediated by PenP.

Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP ß-Lactamase Biosensor.

INTRODUCTION: The use of antibiotics is mandatory in patients during extracorporeal membrane oxygenation (ECMO) support. Clinical studies have shown high variability in the antibiotic concentrations, as well as sequestration of them by the ECMO circuit, suggesting that the doses and/or interval administration used during ECMO may not be adequate. Thus, a fast response sensor to estimate antibiotic concentrations in this setting would contribute to improve dose adjustments. The biosensor PenP has been shown to have a dynamic range, sensitivity and specificity useful for pharmacokinetic (PK) tests in healthy subjects. However, the use of this biosensor in the context of a complex critical condition, such as ECMO during acute respiratory distress syndrome (ARDS), has not been tested. OBJECTIVES: To describe, by using PenP Biosensor, the pharmacokinetic of meropenem in a 24-h animal ARDS/ECMO model. METHODS: The PK of meropenem was evaluated in a swine model before and during ECMO. RESULTS: The PK parameters such as maximum concentration (Cmax), elimination rate constant (Ke), and cleareance (Cl), were not significantly altered during ECMO support. CONCLUSIONS: (a) ECMO does not affect the PK of meropenem, at least during the first 24 h; and (b) PenP has the potential to become an effective tool for making medical decisions associated with the dose model of antibiotics in a critical patient context.

[The impact of a better coordination between emergency and intensive care units in the care of critically ill patients]. / Medicina de urgencia y unidades de cuidados intensivos: Una alianza necesaria en busca de la mejoría de la atención de pacientes críticos.

The need for critical care services is increasing in Chile. Critical care beds and specialists in this area are scarce. In this article we discuss some aspects that hamper the care of critically ill patients from their arrival to the emergency department to their transfer to the ICU. Special emphasis is given to system saturation and its multiple causes. The benefits of an integrative approach between emergency medicine and critical care specialists are highlighted and some solutions are proposed to strengthen this partnership.

[Characteristics and evolution of patients admitted to a public hospital intensive care unit]. / Características y evolución de los pacientes que ingresan a una Unidad de Cuidados Intensivos de un hospital público.

BACKGROUND: The epidemiology of critical patients in Chile could differ from that reported in international studies. AIM: To describe the causes of admission and evolution of patients who were admitted to the ICU (Intensive Care Unit) of a general hospital in Chile in a two-year period (2012-2013). PATIENTS AND METHODS: A retrospective study was carried out using the ICU database. The following variables were registered: admission diagnosis, APACHE II (Acute Physiology and Chronic Health Evaluation), days of mechanical ventilation (MV), ICU length of stay and ICU and hospital survival. RESULTS: We analyzed data from 1075 aged 54 ± 18 years (55% males), representing 75% of the admissions during the study period. The median ICU and MV lengths were 5 and 3 days respectively (92% of patients required MV). APACHE II was 20.5 ± 8.2. The ICU and hospital mortality rate were 19.4% and 31%, respectively. Critical neurological diseases were the most common diagnoses requiring ICU, representing 26.8% of the admissions. No differences were found between 2012 and 2013 in age, APACHE II, ICU or hospital survival. A longer post ICU length of stay was found during 2013, both for patients who survived and those who died at the hospital. CONCLUSIONS: This study highlights the high percentage of patients that required MV and the high percentage critical neurological conditions requiring ICU admission. The characteristics and evolution of patients admitted to the ICU did not differ during 2012 and 2013.

[Necrotizing tracheobronchial aspergillosis in an immunosuppressed patient. Report of one case]. / Aspergilosis traqueobronquial necrotizante en paciente crítico.

Necrotizing tracheobronchitis due to Aspergillus spp is a rare form of invasive aspergillosis. This infection is limited to or predominant in the bronchial tree. The clinical evolution is gradual: from mild non-specific manifestations of acute tracheobronchitis to severe acute respiratory insufficiency determined by a bronchial obstruction syndrome. We report a 38 years old female with systemic lupus erythematosus treated with methylprednisolone and cyclophosphamide. She developed an invasive aspergillosis, severe respiratory failure with predominant tracheobronchial damage and upper respiratory complications.

[Thrombolytic therapy for submassive/ intermediate risk Pulmonary Embolism Evidence and suggestions after PEITHO trial]. / Terapia trombolítica en TEP submasivo/riesgo intermedio: Evidencias y sugerencias post estudio Pulmonary Embolism Thrombolysis (PEITHO).

Therapy for submassive pulmonary embolism (intermediate risk), remains controversial. New evidence has appeared that may help us in the process of decision making. We review the relevant literature, outline prognostic factors, and discuss current recommendations and controversies regarding the available alternatives such as systemic and catheter-directed thrombolytic use.

[Therapeutic monitoring of antibiotics: New methodologies: biosensors]. / Monitorización terapéutica de antibióticos: Nuevas metodologías: biosensores.

The pharmacokinetics of antibiotics, especially in severely ill patients, may be profoundly altered due to multiple pathophysiological changes. Recent studies have shown that empiric dosing recommendations for ICU patients are inadequate to effectively treat a broad range of susceptible organisms and need to be reconsidered. Therapeutic drug monitoring (TDM) is an important mean for optimizing drug utilization and doses for the purpose of improving the clinical effectiveness. However, it is very challenging to quantify plasma antibiotic concentrations in clinical situations as a routine practice, because of the high costs and complexities associated with advanced instrumental techniques. Currently there are not routine and low cost methods to determine the presence and concentration of ß-lactam antibiotics in plasma patients in a clinical setup. Indeed, such analytical methods are based on chromatographic techniques mainly used in research. Here we describe and comment different techniques, focusing on our preliminary experience using biosensors.

[Resuscitation with fluids and blood products in trauma]. / Reanimación con fluidos y hemoderivados en trauma.

The leading cause of preventable death in trauma is uncontrolled bleeding. Some of these deaths may be secondary to the Acute Coagulopathy of Trauma, which is present in 30% of patients on admission to hospital. In recent years, Damage Control Resuscitation has been developed, which aims to give a hemostatic resuscitation and avoid deaths caused by bleeding. This strategy considers control of bleeding with damage control surgery or interventional procedures, early transfusion of all blood products, permissive hypotension and limited use of crystalloids. Several studies have reported that early transfusion of all blood products, with a ratio close to 1:1, may be associated with lower mortality and less requirements of total transfusions in trauma patients at risk of massive bleeding and massive transfusion. These findings must be corroborated in randomized controlled trials, along with determining the optimum ratio between blood products. In stable patients, a restrictive transfusion strategy is safe and appropriate.

[Early determinants of acute kidney injury during experimental intra-abdominal sepsis]. / Determinantes precoces en el desarrollo de injuria renal aguda durante la sepsis abdominal experimental.

BACKGROUND: Sepsis-induced acute kidney injury (AKI) is an early and frequent organ dysfunction, associated with increased mortality. AIM: To evaluate the impact of macrohemodynamic and microcirculatory changes on renal function and histology during an experimental model of intra-abdominal sepsis. MATERIAL AND METHODS: In 18 anaesthetized pigs, catheters were installed to measure hemodynamic parameters in the carotid, right renal and pulmonary arteries. After baseline assessment and stabilization, animals were randomly divided to receive and intra-abdominal infusion of autologous feces or saline. Animals were observed for 18 hours thereafter. RESULTS: In all septic animals, serum lactate levels increased, but only eight developed AKI (66%). These animals had higher creatinine and interleukin-6 levels, lower inulin and para-aminohippurate clearance (decreased glomerular filtration and renal plasma flow), and a negative lactate uptake. Septic animals with AKI had lower values of mean end arterial pressure, renal blood flow and kidney perfusion pressure, with an associated increase in kidney oxygen extraction. No tubular necrosis was observed in kidney histology. CONCLUSIONS: The reduction in renal blood flow and renal perfusion pressure were the main mechanisms associated with AKI, but were not associated with necrosis. Probably other mechanisms, such as microcirculatory vasoconstriction and inflammation also contributes to AKI development.

[Controversies in massive pulmonary embolism]. / Controversias en tromboembolismo pulmonar masivo.

Massive pulmonary embolism (PE) is associated with high mortality. There is still a broad assortment of severity classifications for patients with PE, which affects the choice of therapies to use. The main clinical criteria for defining a PE as massive is systemic arterial hypotension, which depends on the extent of vascular obstruction and the previous cardiopulmonary status. Right ventricular dysfunction is an important pathogenic element to define the severity of patients and short term clinical prognosis. The recommended treatment is systemic thrombolysis, but in centers with experience and resources, radiological invasive therapies through catheters are useful alternatives that can be used as first choice tools in certain cases.

Beta-Lactam Antibiotics Can Be Measured in the Exhaled Breath Condensate in Mechanically Ventilated Patients: A Pilot Study.

Different techniques have been proposed to measure antibiotic levels within the lung parenchyma; however, their use is limited because they are invasive and associated with adverse effects. We explore whether beta-lactam antibiotics could be measured in exhaled breath condensate collected from heat and moisture exchange filters (HMEFs) and correlated with the concentration of antibiotics measured from bronchoalveolar lavage (BAL). We designed an observational study in patients undergoing mechanical ventilation, which required a BAL to confirm or discard the diagnosis of pneumonia. We measured and correlated the concentration of beta-lactam antibiotics in plasma, epithelial lining fluid (ELF), and exhaled breath condensate collected from HMEFs. We studied 12 patients, and we detected the presence of antibiotics in plasma, ELF, and HMEFs from every patient studied. The concentrations of antibiotics were very heterogeneous over the population studied. The mean antibiotic concentration was 293.5 (715) ng/mL in plasma, 12.3 (31) ng/mL in ELF, and 0.5 (0.9) ng/mL in HMEF. We found no significant correlation between the concentration of antibiotics in plasma and ELF (R2 = 0.02, p = 0.64), between plasma and HMEF (R2 = 0.02, p = 0.63), or between ELF and HMEF (R2 = 0.02, p = 0.66). We conclude that beta-lactam antibiotics can be detected and measured from the exhaled breath condensate accumulated in the HMEF from mechanically ventilated patients. However, no correlations were observed between the antibiotic concentrations in HMEF with either plasma or ELF.

Intestinal perforation secondary to blunt inguinal trauma in a soccer player: a case report.

BACKGROUND: Intestinal perforation caused by blunt trauma to an inguinal hernia is a very uncommon event. CASE REPORT: We present the case of a 55-year old man who suffered trauma to the inguinal area while playing soccer and later developed intense abdominal pain with no categorical signs of peritoneal irritation. Computed tomography scan at arrival showed a right inguinal hernia, with partial protrusion of the ileum, inflammatory changes of the mesenteric fat tissue inside the hernial sac, and free intraperitoneal fluid. Several hours later he developed hypotension and fever. An emergency laparotomy was performed, revealing ileum perforation with peritonitis. Intestinal perforation was repaired without intestinal resection. After surgery, the patient developed severe septic shock with multiple organ failure. He recovered without sequelae and was discharged 3 weeks later. CONCLUSION: This case emphasizes the potential clinical complications associated with this condition.

[Prolonged hypothermia in refractory intracranial hypertension. Report of one case]. / Hipotermia intravascular prolongada en un paciente con hipertensión endocraneana refractaria.

The use of hypothermia after cardiac arrest caused by ventricular fibrillation is a standard clinical practice, however its use for neuroprotection has been extended to other conditions. We report a 23-year-old male with intracranial hypertension secondary to a parenchymal hematoma associated to acute hydrocephalus. An arterial malformation was found and embolized. Due to persistent intracranial hypertension, moderate hypothermia with a target temperature of 33°C was started. After 12 hours of hypothermia, intracranial pressure was controlled. After 13 days of hypothermia a definitive control of intracranial pressure was achieved. The patient was discharged 40 days after admission, remains with a mild hemiparesia and is reassuming his university studies.

[Risk stratification of pulmonary thromboembolism]. / Tromboembolismo pulmonar: estratificación de riesgo y dilemas terapéuticos.

The prognosis of pulmonary thromboembolism (PE) is related to the cardiopulmonary reserve of the patient and the magnitude of the embolus that impacts pulmonary circulation. The presence of hemodynamic instability (shock) stratifies a group of patients with high mortality, which should be treated with thrombolysis. Patients without shock but with right ventricular dysfunction can have a dismal evolution and should be managed aggressively. CAT scan, echocardiography and serum markers can be of value to define patients with a higher mortality. The available evidence to define the best diagnostic and therapeutic strategy is scanty, controversial and inconclusive. A good combination of clinical, imaging and biological markers should be defined to identify those patients without shock but with a high rate of complications and mortality, that could benefit from aggressive treatments.

[Pharmacokinetic considerations in critically ill patients]. / Consideraciones farmacocinéticas en el paciente crítico.

Critically ill patients in Intensive Care Units (ICUs) are exposed to multiple procedures and usually require complex treatment regimens. Many of them suffer from comorbidities and different complications such as organ failure, drug-drug interactions, and unusual therapeutic interventions that can produce significant pathophysiologic changes. For that reason, pharmacokinetics for several substances is different to what is described for healthy patients, complicating drug selection and drug dosage to achieve appropriate effects. Low doses may determine a reduction of drug effectiveness and overdoses leading to toxicity. The aim of this paper is to review the pharmacokinetic considerations that must be considered when treating acute ICU patients.