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Fluid resuscitation induces immunomodulation in the critically ill. Current evidence is robust enough to suggest that interventions that induce/prolong inflammatory responses are associated with adverse outcomes in critically ill patients. Therefore, an ‘ideal’ resuscitation fluid in addition to being an effective volume expander should minimize iatrogenic metabolic acidosis and pro-inflammatory mediator expression. While normal saline and perhaps even lactated Ringer’s solution appear to be associated with pro-inflammatory effects, fluids such as hypertonic saline may be associated with anti-inflammatory effects. Solutions such as Hextend may be less likely to be immunomodulating. Further large human studies are required to characterize these effects and their impact on outcomes in the critical care setting.

Volume capnography is a promising non-invasive, inexpensive, breath by breath measurement that has the potential to become an indispensable bedside monitoring tool that can guide the therapeutic process of mechanically ventilated critically ill patients. The better understanding of the pathophysiology of the acutely injured lung on the one hand and the increasing knowledge about the kinetics of CO-exchange on the other has created a growing interest in this technology. Volume capnography provides information about the changes in the lung’s condition and might therefore allow for improved monitoring of complex ventilatory interventions such as lung recruitment and PEEP titration. In addition, the bedside assessment of V helps to identify patients at risk with uneven modes of ventilation and to evaluate their response to different ventilatory strategies. Further studies will help define the true role of volumetric capnography in clinical decision making.

An important limitation with today’s ventilatory management strategies is that while the timing and magnitude of assist is known, it is not possible to determine clinically the amount of unloading and reduction in respiratory drive. Moreover there are no methods to reveal if the ventilator’s assist is delivered when the patient makes the inspiratory effort. To improve accuracy, new monitoring devices for determining respiratory drive and patient-ventilator synchrony are needed. Determination of respiratory drive using diaphragm electrical activity, especially in combination with esophageal pressures can readily help to determine the effect of assist delivery.

The incidence of systemic infection in the intensive care setting has been increasing over the last two decades. While continues to be the commonest species, and has the highest associated mortality, there has been an increase in other species of , such as and , which are more likely to be intrinsically resistant to fluconazole. Therefore, while current IDSA guidelines recommend amphotericin B deoxycholate, caspofungin or fluconazole as primary therapy for adult non-neutropenic patients with candidemia, it is prudent to avoid using fluconazole unless the isolate is known to be sensitive to this drug. Antifungal trials comparing these drugs have focused on patients with candidemia and as a result there is a lack of data on their comparative efficacy in other forms of invasive candidiasis, such as intra-abdominal candidiasis, which can be particularly difficult to treat. There appears to be little to choose between these drugs in terms of efficacy. Caspofungin and fluconazole are less toxic than amphotericin deoxycholate, but the toxicity of amphotericin B is much reduced if a lipid-associated formulation is used.

Combination therapy may provide a much needed means of reducing the morbidity and mortality of invasive candidiasis and reducing the emergence and spread of drug-resistant strains of , which are much more likely to occur on prolonged courses of suboptimal monotherapy. A potential combination is amphotericin B with the antifungal antibody Mycograb. The added cost of such drug combinations will need to be evaluated in the context of the cost of the disease itself, as well as the savings which result from reduced reliance on widespread antifungal prophylaxis and empiric treatment as more effective therapy for proven cases becomes available, and shortened courses of antifungal treatment are possible due to faster resolution of the infection.

Patients with acute brain injury are a unique group of ICU patients. Their indications for intubation and mechanical ventilation are often different from general ICU patients. Therefore, weaning predictors are unique and need to be refined in order to decrease the rate of reintubation while still avoiding prolonged intubation, as both can increase mortality and morbidity. Although tracheostomy may provide a theoretically attractive option for airway management in these patients, potential downsides do exist. Data are limited and the indications and optimal timing for tracheostomy are not well defined. We call for additional studies to investigate this common and important clinical problem.

Respiratory failure after extubation is a frequent complication associated with an increased risk for nosocomial pneumonia, longer length of stay in the hospital, and mortality. Several randomized clinical trials in non-selected patients who have developed respiratory failure after extubation have not demonstrated the benefits of NIV in decreasing the incidence of re-intubation. NIV has even been associated with decreased survival because of a delay in re-intubation of patients treated with NIV. However, in selected patients at high risk, the early use of NIV after extubation seems useful in avoiding respiratory failure after extubation, although the benefits of NIV in improving survival appear restricted to patients with chronic respiratory disorders and hypercapnic respiratory failure during spontaneous breathing. The indication of the early application of NIV after extubation to all hypercapnic patients during spontaneous breathing should be confirmed with a new clinical trial in this specific population.

Since splanchnic impairment of perfusion and oxygenation triggers and perpetuates critical illness, including sepsis and MOF, it is crucial to elucidate the splanchnic effects of common clinical interventions applied in intensive care medicine. Herein, findings of experimental studies may serve to reduce the complexity of splanchnic pathophysiology and generate promising concepts to be tested in the clinical setting. Maybe we have to become familiar with the thought that there is not a single variable guiding our therapy of splanchnic hypoperfusion. Just as we have learned not to judge systemic hemodynamics by a single variable, future splanchnic monitoring tools will enable us to extend our ability to recognize patterns indicative of splanchnic hypoperfusion. Despite major advances in splanchnic monitoring techniques, a combination of easy-to-use and minimally-invasive metabolic and perfusion measurements allowing us to recognize pathophysiologic patterns in splanchnic perfusion and metabolism is not in sight. Ultimately, this concept should enable us to base our therapy on systemic splanchnic circulatory variables to improve outcomes for the critically ill.

The hypermetabolic response that follows a severe burn cannot be halted or reversed, however with the use of prompt surgical intervention to remove the burn eschar, aggressive treatment of developing sepsis, early enteral feeding of high carbohydrate high protein diet together with a program of resistance exercises there are several ways that its effects can be limited. Adding to this an anabolic agent with or without an anticatabolic catecholamine antagonist we will be able to ameliorate the difficult sequelae to an already tragic event. Looking to the future with gene profiling, our understanding of this complex process can only increase and with it better treatment and care for our patients.

In Section 6.1 we sum up with brief indications of the proofs some facts on the open sets in where a differential equation () = with constant coefficients can always be solved. Depending on whether is allowed to be an arbitrary distribution or a function (or a distribution of finite order), we get two classes of admissible open sets depending on . Those which are admissible for every are precisely the genuinely convex sets. However, more general domains are admissible for individual operators . In Section 6.2 we prove by methods close to those used in Section 4.2 that in a pseudo-convex open set in C all equations of the form can be solved. In fact, we prove more general results for operators in a product space × which have this structure with respect to the complex variables. In Section 6.3 we pass to the existence of analytic solutions of equations of the form (,..., ) = in a pseudo-convex open set ⊂ where is analytic. We show that it is precisely in the C convex sets that a solution exists for arbitrary and .

A review of the literature raises the question of how important it is to monitor the quality of sleep in the ICU to avoid clinical consequences such as delirium that seem to be independently associated with worse outcomes, such as prolonged ventilator dependence, ICU length of stay, and hospital length of stay, and is an independent predictor of higher 6-month mortality. Every day spent by ICU patients in a state of delirium is associated with a 10% higher risk of death and worse long-term cognitive function, and delirium is associated with an increase in costs. Taking into consideration the increasing number of elderly patients treated in our ICUs, this burden will rise. Future research should focus on the pathophysiology, cause, and treatment of sleep deprivation and of the occurrence of delirium.