There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao
 2/Fio
 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao
 2/Fi
 o
 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

/pdf/surviving-sepsis-campaign-international-guidelines-for-229kg8suph.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

http://xoomer.virgilio.it/lusebra/NuoviFile/PrevenzioneTVP.pdf

Prevention of venous thromboembolism

Dr John Cade, one of the most distinguished Australian psychiatrists, died in November, 1980. We republish his seminal paper and acknowledge our debt to The Medical Journal of Australia for allowing us to reprint the article from their September 1949 issue.

/pdf/lithium-salts-in-the-treatment-of-psychotic-excitement-ctjkr7b6op.pdf

Lithium salts in the treatment of psychotic excitement.

LITHIUM SALTS enjoyed their hey-day in the latter half of last century when, commencing with their introduction by Garrod, they. were vaunted as curative in gout, and so doubtless in a multitude of other so-called gouty manifestations. This followed the demonstration that lithium urate was the most soluble of the urates. It was shown that if pieces of cartilage with urate deposits were immersed in solutions of sodium, potassium and lithium carbonate, the urate was dissolved first from that piece immersed in the lithium carbonate solution. As time went on and lithia tablets were consumed on an ever-increasing scale for an ever-increasing range of ailments, the toxic and depressant effects were more and more commonly seen. Garrod (1859) wrote of lithium carbonate: "When given internally in doses of from one to four grains dissolved in water, two to three times a day, it produces no direct physiological symptom ... their use does not appear to be attended with any injurious consequences." And certainly, in that dosage, there should never be any toxic symptoms. But about fifty years later cases are reported "of cardiac depression and even dilatation, as a result of excessive and continued consumption of lithia tablets" (The Practitioner, 1907). "Cardiac depression and even dilatation" was perhaps very vague physiology, but the note of warning was clear, also the statement in Squires's "Companion to the British Pharmacopoeia" that "lithia salts upset the stomach very easily" (The Practitioner, 1909). What with the hypothetical cardiac depression and the actual mental depression, nausea and giddiness, the uselessness of lithium in most of the conditions for which it was prescribed, and the fact that there was other, more efficacious treatment in the only disease in which it had been shown to be of some value, it is not surprising that lithium salts have fallen into desuetude. Culbreth (1927) says of lithium bromide that it is the most hypnotic of all bromides. The dosage stated there is the relatively enormous one of 10 to 30 grains. It is not stated how often this huge dose might be repeated each day, but one presumes the traditional two to three times. Squires, too, states that "in epilepsy it is the best of all bromides" and gives the dose more conservatively as five to 15 grains. It is worth noting that the hypnotic action of lithium bromide was thought to be due to the fact that, the atomic weight of lithium being so small, weight for weight, lithium bromide must contain more bromide ion than any other bromide. There is no evidence that the lithium ion was recognized as having a marked sedative action superior in some respects to that of the bromide. But 15 grains of lithium bromide repeated three times a day would soon lead, not to bromide, but to far more dangerous lithium, intoxication, and it is little wonder that it has never found favour in the treatment of epilepsy. It is a pity, because properly used, lithium salts might well be an important addition to the anti-convulsant armamentarium. In the course of some investigations by the writer into the toxicity of urea when injected intraperitoneally into guinea-pigs, it appeared desirable to ascertain whether uric acid enhanced this toxicity. The great difficulty was the insolubility of uric acid in water, so the most soluble urate was chosen--the lithium salt. When an aqueous solution of 8% urea, saturated with lithium urate, was injected, the toxicity was far less than was expected. It looked as if the lithium ion might have been exerting a protective effect. To determine this, more observations were made, lithium carbonate being used instead of lithium urate. An 8% aqueous solution of urea kills five out of ten guinea-pigs when injected intraperitoneally in doses of 1-25 millilitres per ounce of body weight. When 0.5% lithium carbonate in an 8% urea solution was injected in the same dosage, all ten animals survived; and this argued a strong protective function for the lithium ion against the convulsant mode of death caused by toxic doses of urea. …

Lithium salts in the treatment of psychotic excitement. 1949.

The incidence of deep venous thrombosis of the legs (DVT) was studied in 119 critically ill patients by 125I-labeled fibrinogen scanning; the efficacy of low-dose heparin prophylaxis was assessed in a randomized, double-blind study. DVT occurred in 29% of control patients and in 13% of patients receiving heparin 5000 U subcutaneously twice daily. DVT was found mainly in men and was associated with circulatory impairment, respiratory failure and recent vascular or cancer surgery. In a comparison study of medical patients, DVT occurred in 10% untreated and 2% treated. In conclusion, the critically ill are at high risk of venous thromboembolism and low-dose prophylaxis is warranted in those who have no hemostatic impairment.

High risk of the critically ill for venous thromboembolism.

Objective. Pneumonia is an important complication in patients who are intubated and mechanically ventilated, when it is commonly referred to as ventilator-associated pneumonia (VAP). Since VAP may be contributed to by impaired sputum clearance, we studied whether chest physiotherapy designed to enhance sputum clearance decreases the occurrence of VAP.

/pdf/chest-physiotherapy-for-the-prevention-of-ventilator-1si7um93fz.pdf

Chest physiotherapy for the prevention of ventilator-associated pneumonia

ObjectiveTo determine the safety and efficacy of filgrastim (r-metHuG-CSF) in combination with intravenous antibiotics to reduce the rate of mortality in patients with pneumonia and sepsis.DesignThis study was multicenter, double-blind, and randomized.SettingIntensive care unitsPatientsAdult patient

John F. Cade

Papers

Lithium salts in the treatment of psychotic excitement.

Lithium salts in the treatment of psychotic excitement. 1949.

High risk of the critically ill for venous thromboembolism.

Chest physiotherapy for the prevention of ventilator-associated pneumonia

Multicenter, double-blind, placebo-controlled study of the use of filgrastim in patients hospitalized with pneumonia and severe sepsis.