INTRODUCTION

Critically-ill patients in intensive care unit (ICU) usually have deranged physiology, the extent of
which may vary from patient to patient. The physiology is altered due to the disease process itself
(shock, etc.) or due to the therapy (positive pressure ventilation) or both. Many of the ICU therapies
like fluids, vasopressors, and inotropes try to bring the deranged physiology back to normal.
However, feedback loop of these therapies cannot match natural feedback mechanism. Hence, risk
of overtreatment is always a possibility with ICU therapy. While most of ICU therapies are lifesaving,
excessive use of any such therapy can lead to harm. For example, indiscriminate and excessive use of
antibiotics have led to proliferation of resistant bacteria, both in community and hospital. One
inappropriate (not necessarily harmful) therapy may necessitate another therapy, which may have
potential to alter normal physiology. Inappropriate mode of positive pressure ventilation, which
cannot match patients’ complicated demands lead to patient-ventilator dyssynchrony. This leads to
excessive use of sedatives and opioids, which in turn is associated with delayed weaning.

FLUID, A DOUBLE-EDGED SWORD

Fluids are the elixir of hypovolemic shock. Oral rehydration therapy (CRT) is one of the greatest
medical advances of the 20th century. Diarrhea control strategy with ORT has reduced mortality
among children aged less than 5 years by two third.

Almost all patients in ICU need intravenous fluid (IVF). The rate, volume, and type of fluid is
determined by the intent of treatment and type of fluid loss. Fluid boluses with an isotonic
nondextrose containing fluid is the cornerstone of initial resuscitation of patients with septic and
hypovolemic shock. A slightly different composition of fluid can be used as maintenance or as
replacement to compensate for ongoing losses. Administration of NF in unstable patients is largely
empirical unless one is using the goal-directed approach. Timely resuscitation with IVF in initial
stages of shock helps in early reversal of shock and it is largely believed that such therapy probably
prevents the cascade of events leading to multiorgan failure and death.

Similar to other therapies of critical care, IVFs are not free from ill effects. It is now recognized that
excessive IVFs may contribute to new complications like acute respiratory distress syndrome,
abdominal compartment syndrome, coagulopathy, and cerebral edema and may even lead to
worsening of underlying primary disease processes.

Intravenous fluids should be considered as a drug or therapy in a broader aspect. Like a drug, IVF
should be started only after considering its indications, contraindications, and side effects. Just as it
is lifesaving to initiate ventilation in a patient with respiratory failure, it is equally important to wean
the patients from ventilation when primary pathology is resolved. Similarly, it is lifesaving to give
liberal amount of fluid to a patient in septic or hypovolemic shock, it is equally important to stop
giving fluid or even offload the excessive fluid when primary pathology is under control.
PATHOPHYSIOLOGY OF SHOCK

Shock is defined as a state of tissue hypoxia due to reduced oxygen delivery and/or increased oxygen
consumption or inadequate oxygen utilization. About one-third patients in ICU suffer from shock
during their stay. Though shock is commonly classified as distributive, cardiogenic, hypovolemic, and
obstructive, they are not exclusive and most patients will have combination of more than one
particular type. Almost all shocks ultimately manifest as hypotension. However, in early stages,
body’s compensatory mechanisms may play an important role in preventing overt circulatory failure.
Good clinical examination along with meticulous history taking and attention to biochemical markers
will help in detecting this compensatory stage of shock. Timely and appropriate management of
patients in early stages of shock can change outcome of patient.

Pathophysiology of Septic Shock

Among all the shocks in ICU, septic shockis the most common form of shock. A multicenter trial
involving 1,600 patients found that of all shock patients in ICU, the incidence of septic shock was
62%. Etiology of septic shock is multifactorial. lliere is diffuse vasodilation, varying degree of
myocardial depression (septic cardiomyopathy), and redistribution of intravascular fluid which may
be further complicated by failure of the autoregulatory cardiovascular reflexes leading to
hypotension. Myocardial depression due to sepsis is observed both in left and right ventricle.

SOSD PHASES OF TREATMENT OF SHOCK

Fluid therapy forms the mainstay of treatment of almost all shocks. While it is indicated in
hypovolemic and septic shock, it may also help in cardiogenic or obstructive shock as these shocks
may be associated with some degree of hypovolemia or by increasing preload cardiac function may
be optimized better. While we understand that most of the patients with shock will need fluid,
deciding the optimum amount of fluid needed in a particular patient remains a major challenge.
Theoretically, the optimum amount of fluid is that which would increase preload causing maximum
increase in stroke volume (and cardiac output) without causing fluid overload. Unfortunately, this
cannot be estimated accurately at bedside and the monitors designed to identify preload
responsiveness are not always available and have their own sets of limitations.

Vincent and De Backer have proposed a framework about how to resucitate a patient in shock,
according to which treatment of shock can be divided into four phases, with specific therapeutic
goals and monitoring needed in individual phase (Table 1 and Flowchart 1).

Both salvage and optimization phases of treatment constitute initial resuscitation.

Salvage Phase

The first phase of shock treatment is known as salvage phase or rescue phase where the goal of
therapy is to achieve a minimum blood pressure (BP) and cardiac output compatible with immediate
survival. Every patient with life-threatening shock should be resuscitated with these principles.
Initiation of treatment of cause in the form of lifesaving procedures remains one of the most
important aspects of salvage phase. These procedures can be as simple as initiation of appropriate
broad-spectrum antibiotics for possible sepsis and intravenous thrombolysis for ST-elevation
myocardial infarction or complex procedures like drainage for pericardial tamponade or surgery for
source control. Salvage phase mandates a minimal level of monitoring, which can be readily
initiated. However, as patients are vitally unstable, bedside clinical monitoring needs to be intense.
Ongoing continuous or frequent assessments of the patient’s response to therapy are required. If
circumstances allow, one should consider invasive lines like intra-arterial catheter and central
venous catheter. However, in concurrence with the goal of salvage phase, fluid boluses, collection of
blood culture and initiation of broad spectrum antibiotics (in case of suspected sepsis), and other
lifesaving procedures should be given more priority over establishment of invasive monitoring if
both cannot be done simultaneously. This decision should be taken at the bedside based on
patient’s clinical condition, urgency, technical expertise available, level of complexity of the
lifesaving procedures, and hospital setup. One has to understand that “it is the timely interventions
like antibiotics or thrombolysis which save the patient and not measuring arterial or central venous
pressure per se."

Optimization Phase

Stabilization phase addresses to macrocirculation with goal of achieving adequate BP and cardiac
output. This is the first step in ensuring oxygen and nutrient delivery to tissues. Physiologically, it is
difficult to define a ‘normal’ cardiac output; however, adequacy of cardiac output can be judged
from the adequacy of oxygen consumption at cellular level. One should also try to understand
pathophysiology of shock to tailor the therapy. For example, cardiogenic shock will require
optimization primarily with inotropes and afterload reduction, whereas vasodilatory shock will
require optimizations with fluids and vasopressor combination. Interventions targeting
hemodynamic status may help in optimizing cellular oxygen availability in the narrow window of
opportunity. Biochemical markers like lactate clearance rate, venous oxygen saturation (SVO2),
central venous oxygen saturation (ScvO2), venoarterial C02 gap (pCO2 gap) or direct monitoring of
microcirculation may help to achieve this goal. Advanced monitoring tools to assess fluid
responsiveness (pulse pressure variation, stroke volume variation, passive leg raising, end expiratory
occlusion test, change in EtCO2 with volume challenge, etc.) can help in fine-tuning further fluid
therapy. Echocardiography gives valuable information about fluid status, contractility, and aids in
diagnosis of etiology of shock. None of these monitoring tools is without limitation and data
obtained from these monitors should be

correlated along with clinical monitoring to achieve the goal of optimization.

Stabilization Phase

In this stage, as name suggests, patient is hemodynamically stable and does not require as intense
bedside monitoring as that in the salvage stage. Sometimes, with secondary infection or insult,
patient may become unstable again and re-enter salvage phase. Hence, continuous monitoring of
the patient till he or she completely recovers is important. "lhe goal in this stage is to prevent organ
dysfunction that occurs even after hemodynamic optimization. Therefore, key to this phase is organ
support as oxygen supply to the tissues is already optimized. The patient is no more in shock and
primary pathology is already addressed. Aim should be zero or negative fluid balance in this stage. If
shock reappears, patient should enter salvage phase of resuscitation again.

De-escalation Phase

In this last phase of resuscitation, the goal is to gradually wean the patient from vasoactive drugs
and promote fluid elimination. Many patients will start diuresis spontaneously with recovery from
primary insult. In the absence of spontaneous diuresis, clinicians may consider using diuretics to
achieve negative fluid balance with monitoring of serum electrolytes and perfusion indices. In case
of poor response to diuretics, one may also consider use of ultrafiltration.

One has to understand that patients in critical care unit need not always enter this framework of
resuscitation. Patients who are grossly hypotensive, requiring fluid resuscitation, will enter in the
salvage phase needing fluid boluses. Other patients who do not have overt hypotension but are at
risk for shock or having early compensated shock may enter at the optimization phase. In
optimization phase, assessment of fluid responsiveness using fluid challenges or other dynamic
variables rather than fluid boluses are the initial management. Once clinical condition improves,
patient should proceed to stabilization and de-escalation where priority is prevention of adverse
effects of fluids. It is not necessary that all patients will follow the same sequence. Patient’s course
in ICU is a dynamic process where patients may experience temporary deterioration, for example, as
a consequence of a secondary infection, blood loss, and surgical complication, necessitating
switching from a stabilization strategy back to optimization or salvage stage.

UNDERSTANDING TERMINOLOGIES IN FLUID THERAPY

The terms fluid bolus and fluid challenge are not interchangeable. Fluid bolus is given when clinician
is sure that patient is hypovolemic and will respond positively to fluid by increasing cardiac output
and oxygen delivery. On the other hand, fluid challenge is a diagnostic as well as therapeutic
intervention, which is done when clinician is not sure that patient will respond positively to fluid.

Fluid Bolus
It is a rapid infusion of relatively large volume of fluid to correct absolute or relative fluid deficit. It
typically includes the infusion of at least BOO-1,000 mL of fluid over a period of 15-30 minutes.
Surviving sepsis campaign 2016 guidelines recommend at least 30 mL/ kg of intravenous crystalloid
fluid to be given within the first 3 hours for the resuscitation from sepsis induced hypoperfusion.

Fluid Challenge

In 30 minutes, 500 mL of crystalloids can be given. Smaller fluid challenges of 100-200 mL over 5-10
minutes can also be used. With fluid challenge, patient ShouId be reassessed to coniirm whether
clinical endpoints or pressure safety limits are reached. Fluid challenge can help in optimization of
tissue perfusion while minimizing the risk of fluid overload Without advanced hemodynamic
monitoring.

Thus, a “fluid bolus” is administration of large volumes of fluid without close monitoring rapidly for
rescue and a "fluid challenge" is a test where a modest amount of fluid is given more slowly and the
effects are assessed, to prevent inadverent fluid overload.
ILLUSTRATION WITH CASE STUDY:

A 50 year old male weighing approximately 60 kg, with history of duodenal ulcer presents to
emergency department with abdominal pain since last 4 days. Pain worsened since last 10 hours and
he has had three episodes of vomiting in last 9 hours. On presentation, his heart rate was 148/min,
Respiratory rate 38/ min. and BP was 60/40 (MAP 47) mmHg. He had cold and calmmy extremities
and his abdomen was tender to touch. He had not passed urine in the last 8 hours,

He did not have any other medical condition.

How Will You Resuscitate this Patient?

SOSD Approach

This patient is in life-threatening shock. Principles of salvage phase of resuscitation should be

adopted. Since this patient is nonhypertensive, mean arterial pressure (MAP) of 65 mmHg is a
reasonable target. Patient’s history and clinical condition suggest possibility of perforative
peritonitis. Patient should be immediately resuscitated with isotonic fluid 30 mL/kg according to
surviving sepsis 2016 guidelines.

Emergency management was initiated with oxygen supplementation, and peripheral intravenous
access was secured with two wide bore 16 G cannulae. Monitoring with continuous
electrocardiogram (ECG), noninvasive BP, and pulse oximeter was initiated. Blood was collected for
culture, hemogram, biochemistry, and blood grouping and cross matching. A fluid bolus of Ringers
lactate (RL) 1 L was given over next 30 minutes. Simultaneously, the patient was intubated with 8.0
number cuffed endotracheal tube and initiated on volume assisted mechanical ventilation (settings
according to lung protective ventilation). The patient was also started on empirical antibiotic
piperacilline-tazobactum 4.5 g four times daily. Meanwhile, surgical reference was obtained
suspecting duodenal perforation and peritonitis. X-ray abdomen in sitting position was obtained in
emergency department (ED), which confirmed gas under diaphragm. After infusion of 1 L of RL
solution, patients MAP was 55 mmHg with pulse rate of 133/ min. Another fluid bolus of 500 mL RL
was given over next 20 minutes, patients left radial artery was cannulated for continuous direct
arterial pressure monitoring and arterial blood gas (ABG) was obtained. Urinary bladder was
catheterized which drained 125 mL dark colored urine. Meanwhile, surgeons agreed to take up this
patient for emergency laparotomy once patient was in a relatively stable condition. After infusion of
2 L of RL, patients MAP had come up to 58 mmHg (90/40 mmHg). Patients ABG report showed
lactates of 8.5 mmol/ L. The patient was wheeled in operation theatre (OT) with fifth RL on flow. In
OT, his right internal jugular vein was cannulated under ultrasound guidance and he was also started
on noradrenaline at 0.06 pg/kg/min to achieve an MAP of 65 mmHg.

Here, the patient has been salvaged from life-threatening shock. This can be optimized further with
optimization phase of intravenous fluid therapy. Hourly urine output monitoring was initiated as a
clinical indicator of cardiac output. Since patient has both central line and arterial line in place, one
can use either fluid challenge/ pulse pressure variation (PPV) or can consider using minimally
invasive cardiac output monitor to decide fluid responsiveness and plan further fluid therapy
accordingly. If invasive pressure lines have not been inserted in the salvage phase, they should be
inserted now. Lactate level and its clearance may be a fair guide for fluid therapy. Exploratory
laparotomy for source control at earliest is crucial.

Laparotomy revealed perforated duodenal ulcer with almost 1.5 L of pus and fecal matter in
peritoneal cavity. A thorough wash was given, perforation was repaired with omental patch,
nasojejunal and nasogastric tubes were placed, and two large bore drains were kept near
perforation site. During the course of surgery, patient received another 1.5 L fluid in OT and
noradrenaline was continued to maintain MAP more than 65 mmHg. Patient was shifted to ICU for
further management.

Thus, since arrival to ED, the patient has been stabilized with 4.0 L of crystalloids, vasopressor
support with noradrenaline and ventilatory support. More importantly, patient has received
appropriate antibiotics and adequate source control.

On arrival to ICU, patient’s BP was 104/52 (MAP: 69) mmHg, pulse rate of 130/min with
noradrenaline 0.06 ug/kg/min. Patient had central venous pressure of 8 mmHg. Bedside ECG
revealed normal cardiac contractility and his repeat lactate level was 7.8 mmol/L. PPV of 17 even
with low tidal volume ventilation (6 mL/kg) suggested fluid responsiveness. After two fluid boluses of
250 mL over 15 minutes, PPV dropped to 11. Tidal volume challenge test was also negative for fluid
responsiveness. Repeat ABG after 4 hours showed lactates of 4.2 mmol/ L, and by this time, the
urine output had increased to 20~25 mL/h.

Normalization of the BP does not guarantee adequate perfusion of tissues. The cardiac output may
still be inadequate and it may need to be optimized further. If facilities are available, one may use
functional hemodynamic monitoring to assess fluid responsiveness. In the absence of these
monitors, fluid challenge using central venous access with preset goals and safety limits can be used.

In presence of low tidal volume, sensitivity of PPV as predictor of fluid responsiveness decreases,
one can use tidal volume challenge to see if patient is fluid responsive, which has shown to work in
patients with compliant lungs. In case of drop in BP or cardiac output, one should reassess fluid
responsiveness before escalating vasopressor support. Therefore, optimization phase will continue
till optimization of cellular oxygen delivery and may last for days in some complicated cases.

On the next day, lactates were 1.7 mmol/ L, and ScVO2 was 76%. His urine output was around 25-30
mL/ h. As patient had recovered from shock, process of weaning from mechanical ventilator was
initiated. Dexmedetomidine infusion was started for combative and agitated behavior of patient
after stopping sedation.
Patient is hemodynamically stable on minimal vasopressor support and normal lactates suggesting
optimum oxygen delivery to tissues. In this phase, known as stabilization phase, treatment goal is to
support other organ systems as patient is already hemodynamically optimized.

Feeding through nasojejunal route was initiated. His hemodynamic parameters showed him to be
fluid unresponsive. Patient continued to have low urine output and had significant positive fluid
balance. Attempts to wean him off mechanical ventilation failed. As patient’s hemodynamic
parameters continued to improve, he was weaned off noradrenaline support over the next 24 hours.
Over the next 3 days, with help of diuretics, patient was made 3 L negative in concurrence with the
goals of de-escalation phase. On 6th postoperative day, patient was obeying commands with eye
contact and good cough reflex. He was successfully liberated from mechanical ventilation,
extubated, and discharged to ward on 8th postoperative day of his emergency laparotomy.

Patient can be de-escalated from fluid with either diuresis or dialysis. In most patients, spontaneous
diuresis occurs as their condition improves. In such situations, one should monitor serum
electrolytes at frequent interval and restrict amount of fluid infused. Sometimes, diuretics are
needed to achieve negative fluid balance as in this case. Occasionally, patient may need dialysis for
iluid removal.

CONCLUSION

Intravenous fluid administration is a lifesaving intervention in patients with hypovolemic shock.

Timely fluid resuscitation saves patient from tissue hypoxia and organ dysfunction and possibly
reduces mortality. A patient in life-threatening shock should be salvaged with fluid boluses to
achieve minimum BP and cardiac output compatible with immediate survival. If there is doubt about
favorable response to fluid, a fluid challenge should be given instead of fluid boluses. Equally
important is immediate management of underlying pathology of shock. Once life-threatening shock
is corrected, hemodynamic status should be optimized further with better monitoring tools that will
help optimize tissue oxygen delivery and reduce chances of inadvertent fluid overload. Once patient
stabilizes, monitoring should continue until patient recovers. In event of reappearance of shock at
any stage, salvage and optimization should be reinitiated. As patient starts recovering from primary
insult and as vasoactive drug requirements start coming down, clinician should consider active de-
escalation of fluid therapy with the help of restriction of fluid and accelerated fluid elimination Via
diuresis and dialysis whenever appropriate. Like all drug therapy, intravenous fluid therapy is
lifesaving when given at an appropriate time and in an appropriate dose, otherwise there is a risk of
significant damage. The present SOSD concept gives a roadmap not only of initiating and maintaining
fluid therapy but also more importantly, weaning from it.