Definisi Encephalopathy

Encephalopathy adalah istilah yang berarti penyakit, kerusakan, atau malfungsi otak. Encephalopathy dapat menyajikan spektrum
yang sangat lebar dari gejala-gejala yang mencakup dari yang ringan, seperti beberapa kehilangan memori atau perubahan-
perubahan kepribadian yang hampir tidak kentara, sampai yang parah, seperti dementia, seizures, koma, atau kematian. Pada
umumnya, encephalopathy dimanifestasikan oleh keadaan mental yang berubah yang adakalanya ditemani oleh manifestasi-
manifestasi fisik (contohnya, koordinasi yang buruk dari gerakan-gerakan anggota tubuh).
Istilah encephalopathy adalah sangat lebar dan pada kebanyakan kasus-kasus, didahului oleh beragam istilah-istilah yang
menggambarkan sebab, penyebab, atau kondisi-kondisi khusus dari pasien yang menjurus pada malfungsi otak. Contohnya,
anoxic encephalopathy berarti kerusakan otak yang disebabkan oleh kekurangan oksigen, dan hepatic encephalopathy berarti
malfungsi otak yang disebabkan oleh penyakit hati. Sebagai tambahan, beberapa istilah-istilah lain yang menggambarkan kondisi-
kondisi tubuh atau gejala-gejala yang menjurus pada set yang spesifik dari malfungsi-malfungsi otak. Contoh-contoh dari ini adalah
metabolic encephalopathy dan Wernicke's encephalopathy (Wernicke's syndrome). Ada lebih dar 150 istilah-istilah yang
berbeda yang memodifikasi atau mendahului "encephalopathy" dalam literatur medis.
Penyebab Encephalopathy
Penyebab-penyebab dari encephalopathy adalah kedua-duanya banyak dan bervariasi.
Beberapa contoh-contoh dari penyebab-penyebab encephalopathy termasuk:
infeksi-infeksi (bakteri-bakteri, virus-virus, parasit-parasit, atau prions),
anoxia (kekurangan oksigen pada otak),
konsumsi alkohol,
gagal hati,
gagal ginjal,
penyakit-penyakit metabolik,
tumor-tumor otak,
banyak tipe-tipe kimia yang beracun,
perubahan-perubahan pada tekanan dalam otak, dan
nutrisi yang buruk.
Contoh-contoh ini tidak mencakup semua penyebab-penyabab yang berpotensi dari encephalopathy namun didaftar untuk
menunjukan batasan yang lebar dari penyabab-penyebab.
Meskipun banyak penyebab-penyebab dari encephalopathy diketahui, mayoritas dari kasus-kasus timbul dari beberapa kategori-
kategori utama:
1. infeksi,
2. kerusakan hati,
3. anoxia, dan
4. gagal ginjal.
Gejala-Gejala Dari Encephalopathy
Meskipun penyebab-penyebab encephalopathy banyak dan bervariasi, paling sedikit satu gejala yang hadir pada semua kasus-
kasus adalah keadaan mental yang berubah. Keadaan mental yang berubah mungkin hampir tidak kentara dan berkembang
secara perlahan melalui waktu bertahun-tahun atau menjadi sangat jelas dan berkembang secara cepat (contohnya, anoxia otak
menjurus pada koma atau kematian dalam beberapa menit).Seringkali, gejala-gejala dari keadaan mental yang berubah dapat
hadir sebagai kecerobohan (kurang perhatian), keputusan yang buruk, atau koordinasi yang buruk dari gerakan-gerakan.
Gejala-gejala lain yang mungkin terjadi termasuk:
kelesuan,
dementia,
seizures,
tremor-tremor,
kejang otot, dan
koma.
Sering keparahan dan tipe dari gejala-gejala berhubungan pada keparahan dan penyebab dari penyakit atau kerusakan otak.
Contohnya, kerusakan hati yang diinduksi alkohol (alcoholic cirrhosis) dapat berakibat pada gemetar-gemetar tangan yang tidak
sukarela (asterixis), sementara anoxia yang parah (kekurangan oksigen) mungkin berakibat pada koma dengan tidak ada
gerakan.
Mendiagnosa Encephalopathy
Diagnosis dari encephalopathy biasanya dilakukan dengan tes-tes klinik yang dilakukan selama pemeriksaan fisik (tes-tes status
mental, tes-tes memori, tes-tes koordinasi) yang mendokumentasikan keadaan mental yang berubah. Dengan kebanyakan kasus-
kasus, penemuan-penemuan pada tes-tes klinik mendiagnosa atau menganggap mendiagnosa encephalopathy. Biasanya, diagnosis
terjadi ketika keadaan mental yang berubah menemani diagnosis primer yang lain seperti penyakit hati kronis, gagal ginjal,
anoxia, atau banyak diagnosa-diagnosa lainnya.
Dengan konsekwen, dokter-dokter mungkin menggunakan beberapa tes-tes yang berbeda pada saat yang bersamaan untuk
mendiagnosa keduanya kondisi primer (penyebab dari encephalopathy) dan encephalopathy sendiri. Pendekatan pada diagnosis ini
dilakukan oleh kebanyakan dokter-dokter, karena banyak dokter-dokter memandang encephalopathy sebagai komplikasi yang
terjadi karena persoalan kesehatan utama yang mendasarinya. Tes-tes yang paling sering digunakan didaftar dibawah dengan
beberapa dari penyebab-penyebab primer utama tes-tes mungkin membantu mendiagnosa:
Pemeriksaan darah komplit atau complete blood count atau CBC (infeksi-infeksi, kehilangan darah)
Tekanan darah (tekanan darah tinggi atau tekanan darah rendah)
Tes-tes metabolik (tingkat-tingkat darah dari elektrolit-elektrolit, glucose, lactate, ammonia, oksigen, dan tingkat-tingkat
enzim hati)
Obat-obat atau tingkat-tingkat racun (alkohol, cocaine, amphetamines, dan banyak lain-lainnya)
Pembiakan-pembiakan dan analisa-analisa darah dan cairan tubuh (infeksi-infeksi dari banyak tipe-tipe)
Creatinine (fungsi ginjal)
CT dan MRI scans (pembengkakan otak, kelainan-kelainan anatomi, infeksi-infeksi)
Doppler ultrasound (aliran darah yang abnormal ke jaringan-jaringan, abscesses)
Encephalogram atau EEG (kerusakan otak, pola-pola gelombang otak yang abnormal)
Auto-antibody analysis (dementia yang disebabkan oleh antibodi-antibodi yang menghancurkan neuron-neuron)
Daftar ini belum selesai (habis), dan tidak semua dari tes-tes diatas perlu dilakukan untuk mencapai diagnosis; pengujian khusus
biasanya diperintahkan oleh dokter yang merawat menurut gejala-gejala dan sejarah dari pasien.
Perawatan Untuk Encephalopathy
Perawatan dari encephalopathy bervariasi dengan penyebab-penyebab primer yang mendasarinya; dengan konsekwen, tidak
semua kasus-kasus dari encephalopathy dirawat secara sama. Perawatan-perawatan yang terbaik didisain oleh dokter yang
merawat sekali diagnosis primer pasien dibuat. Perawatan-perawatan bervariasi sangat tinggi karena penyebab-penyebabnya
begitu berbeda.
Contoh-contoh dapat menunjukan seberapa bedanya "perawatan encephalopathy" mungkin berubah menurut penyebabnya:
Anoxia jangka pendek (biasanya kurang dari dua menit): terapi oksigen
Anoxia jangka panjang: rehabilitasi
Keracunan alkohol jangka pendek: cairan-cairan IV (intravena) atau tidak ada terapi
Penyalahgunaan alkohol jangka panjang (sirosis atau gagal hati kronis: oral lactulose, diet rendah protein,
antibiotik-antibiotik
Uremic encephalopathy (disebabkan oleh gagal ginjal): mengkoreksi penyebab fisiologi yang mendasarinya, dialysis,
transplantasi ginjal
Diabetic encephalopathy: glucose untuk merawat hypoglycemia, pengeluaran glucose darah untuk merawat
hyperglycemia
Hypo- atau hypertensive encephalopathy: menaikan tekanan darah (untuk hipotensi) atau mengurangi (untuk hipertensi)
Kunci untuk merawat segala encephalopathy adalah untuk mengerti penyebab dasar dan jadi mendisain rencana perawatan untuk
mengurangi atau menghilangkan penyebab-penyebabnya. Ada satu tipe encephalopathy yang sulit atau tidak mungkin untuk
dirawat; ia adalah static encephalopathy (keadaan mental yang berubah atau kerusakan otak yang permanen). Yang terbaik
yang dapat dilakukan dengan static encephalopathy adalah, jika mungkin, untuk mencegah kerusakan lebih jauh dan menerapkan
rehabilitasi untuk megizinkan individu melakukan pada tingkat fungsi setinggi mungkin.
Komplikasi-Komplikasi Dari Encephalopathy
Komplikasi-komplikasi dari encephalopathy bervariasi dari tidak ada gangguan-gangguan mental sampai gangguan-gangguan
mental yang sangat besar yang menjurus pada kematian. Komplikasi-komplikasi dapat menjadi serupa pada beberapa kasus-kasus.
Juga, banyak penyelidik-penyelidik mempertimbangkan encephalopathy adalah komplikasi yang timbul dari persoalan kesehatan
primer atau diagnosis primer.
Komplikasi-komplikasi tergantung pada penyebab utama dari encephalopathy dan dapat diilustrasikan dengan mengutip beberapa
contoh-contoh dari keberagaman yang luas dari penyebab-penyebab:
Hepatic (hati) encephalopathy (pembengkakan otak dengan herniation, koma, kematian)
Metabolic encephalopathy (sifat lekas marah, kelesuan, depresi, gemetar-gemetar; adakalanya koma atau kematian)
Anoxic encephalopathy (batasan yang luas dari komplikasi-komplikasi, dari tidak ada pada anoxia jangka pendek
sampai perubahan-perubahan kepribadian, kerusakan otak yang parah sampai kematian pada kejadian-kejadian anoxic
jangka panjang)
Uremic encephalopathy (kelesuan, halusinasi-halusinasi, pingsan, kejang otot, seizures, kematian)
Hashimoto's encephalopathy (kebingungan, ketidaktoleriran panas, dementia)
Wernicke's encephalopathy (kebingungan mental, kehilangan memori, kemampuan yang berkurang untuk
menggerakan mata-mata)
Bovine spongiform encephalopathy atau "Mad Cow disease" (ataxia, dementia dan myoclonus atau kejang otot
tanpa segala irama atau pola)
Shigella encephalopathy (sakit kepala, leher yang kaku, delirium, seizures, koma)
Kasus-kasus infeksius dari pediatric encephalopathy (sifat lekas marah, pemberian makan yang buruk, hypotonia
atau floppy baby syndrome, seizures, kematian)
Cara yang terbaik untuk mengerti komplikasi-komplikasi yang berpotensi adalah untuk mendiskusikan ini dengan dokter yang
mendiagnosa yang dapat mendiskusikan persoalan-persoalan yang mungkin yang berhubungan dengan penyebab-penyebab yang
spesifik dari tipe encephalopathy.
Prognosis (Harapan) Untuk Encephalopathy
Prognosis untuk pasien dengan encephalopathy tergantung pada penyebab-penyebab awalnya dan, pada umumnya, lama
waktunya untuk membalikan, menghentikan, atau menghalangi penyebab-penyebab itu. Dengan konsekwen, prognosis bervariasi
dari pasien ke pasien dan mencakup dari pemulihan sepenuhnya sampai ke prognosis yang buruk yang seringkali menjurus pada
kerusakan otak yang permanen atau kematian. Satu contoh yan baik dari prognosis yang bervariasi sangat tinggi ini adalah pasien-
pasien yang mendapat encephalopathy dari hypoglycemia. Jika pasien-pasien dengan hypoglycemia diberikan glucose pada tanda-
tanda pertama dari encephalopathy (contohnya, sifat lekas marah, kebingungan yang ringan), kebanyakan pasien-pasien sembuh
sepenuhnya. Penundaan-penundaan pada pembetulan hypoglycemia (berjam-jam sampai berhari-hari) mungkin menjurus pada
seizures atau koma yang mungkin dihentikan oleh perawatan dengan kesembuhan sepenuhnya atau sebagian (kerusakan otak
permanen yang minimal). Penundaan yang lama atau beragam penundaan-penundaan pada perawatan dapat menjurus pada
prognosis yang buruk dengan kerusakan otak yang ekstensif, koma, atau kematian.
Meskipun gejala-gejala dan batasan waktu bervariasi dengan lebar dari pasien ke pasien dan menurut penyebab-penyebab awal
dari encephalopathy (lihat diatas bagian-bagian untuk contoh-contoh dari penyebab-penyebab), prognosis dari setiap penyebab
biasanya mengikuti pola yang digambarkan pada contoh hypoglycemic diatas dan tergantung pada luas dan kecepatan dengannya
penyebab yang mendasarinya dirawat. Dokter atau team dari dokter-dokter yang merawat penyebab yang mendasari
encephalopathy dapat menawarkan informasi yang terbaik pada prognosis individu.
Mencegah Encephalopathy
Banyak kasus-kasus dari encephalopathy dapat dicegah. Kunci pada pencegahan adalah menghentikan atau membatasi
kesempatan mengembangkan apa saja dari banyak penyebab-penyebab encephalopathy. Jika encephalopathy berkembang, lebih
cepat penyebab yang mendasarinya dirawat, lebih mungkin bahwa encephalopathy parah dapat dicegah.
Contoh-contoh dari pencegahan (dan situasi-situasi untuk dihindari) didaftar dibawah:
Diabetic encephalopathy: lakukan pemeriksaan-pemeriksaan glucose harian dan selalu periksa bahwa pemasukan
insulin adalah dosis yang benar.
Hepatic encephalopathy: hindari keracunan alkohol, overdosis-overdosis obat, dan suntikan-suntikan IV dari obat-obat
terlarang.
Anoxic encephalopathy: cegah tersendak makanan, hindari kelakuan yang berisiko yang dapat menjurus pada trauma
kepala dan leher, hindari paparan pada karbon monoksida.
Hypertensive encephalopathy: monitor tekanan darah; konsumsi obat-obat antihipertensi seperti yang diarahkan dan
jangan menghentikan obat-obat atau merubah obat-obat tanpa mengkonsultasi dokter anda.
Infectious encephalopathy: hindari kontak fisik dengan individu-individu yang diketahui terinfeksi dengan organisme-
organisme yang mungkin menyebabkan encephalopathy seperti N. meningitidis atau Shigella.
Uremic encephalopathy: jangan melewatkan atau menghindari dialysis yang telah dijadwalkan, konsumsi semua obat-
obat seperti yang diarahkan dan mempunyai penilaian-penilaian yang seringkali dari status mental.
Metode-metode untuk pencegahan encephalopathy kira-kira sama banyaknya seperti penyebab-penyebab yang mendasarinya;
bagaimanapun, beberapa kasus-kasus dari encephalopathy mungkin tidak dapat dicegah (contohnya, congenital dan accidental
traumatic encephalopathy).
ARAS(Ascending Reticular Activating System)/KESADARAN




Komponen dari sistem ekstrapiramidal ini terdiri dari:
1. Korteks serebri (area 4, 6 dan 8)
2. Basal Ganglia, terdiri dari:
a. Korpus striatum:
i. Nukleus kaudatus
ii. Nukleus lentiformis: Globus pallidus
Putamen
b. Corpus Luysi (nukleus subtalamikus)
c. Substansia nigra
d. Talamus (nukleus ventrolateralis talami)
3. Nukleus rubra
4. Substansia retikularis batang otak
5. Serebelum

Tanda-tanda utama dari lesi ekstrapiramidalis adalah gangguan tonus otot (distonia) dan gangguan gerakan
involunter (hiperkinesia, hipokinesia, akinesia) yang tidak ada selama tidur. Dibedakan dalam 2 sindrom klinis:
1. SINDROM HIPOKINESIA-HIPERTONIA
Sindrom ini secara klasik ditemukan pada paralisis agitans atau penyakit parkinson. Kerusakan jaringan dalam
penyakit ini adalah degeneratif dan bersifat herediter dan mengakibatkan hilangnya neuron yang mengandung
melanin dari substansia nigra dan neuron dopaminergik yang berhubungan dengan striatum. Proses penyakit
ini biasanya bilateral, tetapi bila terjadi secara unilateral tanda klinis akan melibatkan separuh tubuh
kontralateral. Sindrom parkinson jika merupakan gejala sisa lanjut dari ensefalistis letargik maka disebut
parkinsonisme postensefalitis. Selain itu dapat disebabkan oleh arteriosklerosis serebri, trauma, sifilis serebri
atau asupan yang lama fenotiazin dan reserpin.
Paralisis agitans atau penyakit Parkinson ditandai oleh 3 tanda utama yaitu:
a. Akinesia
Sukar memulai gerakan, gerakan lamban, pasien pertama harus mengambil langkah pendek-pendek, sukar
menghentikan gerakan berjalan secara mendadak, sebelum dapat berhenti pasien harus melangkah beberapa
langkah ekstra, karena persarafan kontranya terhambat.
b. Rigor
Otot tidak dapat direlaksasikan. Dalam gerakan pasif seseorang dapat merasakan bahwa tonus dari otot
antagonis menurun secara bertahap dan tidak sama terus (cogwheel phenomenon). Kepala yang diangkat
pada orang yang berbaring jika dilepaskan secara mendadak tidak jatuh seperti biasanya tetapi turun secara
bertahap kembali ke bantal (Head dropping test).
c. Tremor
Tremor bersifat lambat 4-8 gerakan perdetik, bersifat ritmik, tremor terjadi saat istirahat (resting tremor)
tetapi hilang saat tidur. Gerakan seperti menggulung pil atau menghitung uang.

2. SINDROM HIPERKINESIA-HIPOTONIA
Sindrom ini terjadi bila neostriatum mengalami kerusakan. Kadang-kadang lesi seperti ini disertai oleh lesi
lainnya dalam globus palidus, talamus dan korteks serebri. Hiperkinesia mungkin disebabkan oleh hilangnya
neuron inhibisi dari neostriatum yang berdesenden ke palidum dan substansia nigra sehingga menimbulkan
eksitasi yang berlebihan dari neuron-neuron sistem berikutnya yang lebih rendah. Hiperkinesia yang terjadi
dapat berupa :
a. Atetosis.
Gangguan kinetik ini biasanya disebabkan oleh kerusakkan perinatal dari korpus striata. Gerakan volunter
berubah hebat yang mungkin melibatkan wajah dan lidah sehingga menyebabkan wajah menyeringai dengan
gerakan yang abnormal.
b. Korea.
Sindrom korea ditandai secara khas oleh sentakan involunter yang pendek dan cepat dan menghasilkan
berbagai pola gerakan.
Gerakan korea yang sering terlihat pada anak-anak sebagai korea minor atau korea sydenham atau tarian St.
Vitus . Merupakan gangguan yang akut,biasanya hilang sendiri dan sering berkaitan erat dengan demam
rematik (korea infeksiosa). Bila terjadi pada kehamilan muda disebut korea gravidarum.
Korea Huntington suatu penyakit degeneratif dominan, herediter yang biasanya timbul pada usia
pertengahan-dewasa.
c. Tortikolis spasmodik dan distonia torsi
Tortikolis spasmodik suatu kelainan tonik terdiri dari kontraksi spasmodik dari otot-otot dalam daerah leher
yang menghasilkan gerakan kepala menoleh dan memutar involunter dan lambat.
Distonia torsi ditandai dengan secara khas oleh gerakan memutar dan menoleh yang agak berlebihan pada
tubuh dan ekstremitas proksimal. Penyebabnya dapat cedera waktu lahir, kernikterus, korea Huntington
d. Sindrom balistik
Sindrom ini biasanya terjadi sebagai hemibalismus. Gerakan involunter ditandai secara khas oleh gerakan
melempar dan menjangkau keluar yang kasar terutama otot-otot bahu dan pelvis.
Gangguan ini merupakan akibat dari kerusakan akut nukleus subtalamik dari luys dan hubungan dengan
bagian lateral palidum. Hemibalismus yang terjadi kontralateral dari lesi.

Sepsis
From Wikipedia, the free encyclopedia
Jump to: navigation, search
For the genus of flies of this name, see Sepsidae.
Sepsis is a serious medical condition that is characterized by a whole-body inflammatory state (called a systemic
inflammatory response syndrome or SIRS) and the presence of a known or suspected infection.
[1][2]
The body may
develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other
tissues. A lay term for sepsis is blood poisoning, more aptly applied to septicemia (a deprecated term), below.
Septicemia (also septicaemia or septicmia [septicmia],
[3]
or erroneously septasemia and septisema) is a
related but deprecated medical term referring to the presence of pathogenic organisms in the bloodstream,
leading to sepsis.
[4]
The term has not been sharply defined. It has been inconsistently used in the past by medical
professionals, for example as a synonym of bacteremia, causing some confusion. The present medical consensus is
therefore that the term "septicemia" is problematic and should be avoided.
[2]

Sepsis is usually treated in the intensive care unit with intravenous fluids and antibiotics. If fluid replacement is
insufficient to maintain blood pressure, specific vasopressor medications can be used. Mechanical ventilation and
dialysis may be needed to support the function of the lungs and kidneys, respectively. To guide therapy, a central
venous catheter and an arterial catheter may be placed. Sepsis patients require preventive measures for deep
vein thrombosis, stress ulcers and pressure ulcers, unless other conditions prevent this. Some patients might
benefit from tight control of blood sugar levels with insulin (targeting stress hyperglycemia), low-dose
corticosteroids or activated drotrecogin alfa (recombinant protein C).
[5]

Contents
1 Terminology
2 Signs and symptoms
3 Diagnosis
o 3.1 Neonatal sepsis
4 Treatment
o 4.1 Adults and children
o 4.2 Neonates
5 Prognosis
6 Epidemiology
7 Research
o 7.1 Inflammatory signal blocker
o 7.2 Nitric oxide
8 See also
9 References
10 External links
Terminology
Severe sepsis occurs when sepsis leads to organ dysfunction, low blood pressure (hypotension), or insufficient
blood flow (hypoperfusion) to one or more organs (causing, for example, lactic acidosis, decreased urine
production, or altered mental status). Sepsis can lead to septic shock, multiple organ dysfunction syndrome
(formerly known as multiple organ failure), and death. Organ dysfunction results from sepsis-induced hypotension
(< 90 mmHg or a reduction of 40 mmHg from baseline) and diffuse intravascular coagulation, among other
things.
Bacteremia is the presence of viable bacteria in the bloodstream. Likewise, the terms viremia and fungemia
simply refer to viruses and fungi in the bloodstream. These terms say nothing about the consequences this has on
the body. For example, bacteria can be introduced into the bloodstream during toothbrushing.
[6]
This form of
bacteremia almost never causes problems in normal individuals. However, bacteremia associated with certain
dental procedures can cause bacterial infection of the heart valves (known as endocarditis) in high-risk patients.
[7]

Conversely, a systemic inflammatory response syndrome can occur in patients without the presence of infection,
for example in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis.
[2]

Signs and symptoms
In addition to symptoms related to the provoking infection, sepsis is characterized by presence of acute
inflammation present throughout the entire body, and is, therefore, frequently associated with fever and elevated
white blood cell count (leukocytosis) or low white blood cell count and lower-than-average temperature, and
vomiting
[citation needed]
. The modern concept of sepsis is that the host's immune response to the infection causes
most of the symptoms of sepsis, resulting in hemodynamic consequences and damage to organs. This host
response has been termed systemic inflammatory response syndrome (SIRS) and is characterized by
hemodynamic compromise and resultant metabolic derangement. Outward physical symptoms of this response
frequently include a high heart rate (above 90 beats per minute), high respiratory rate (above 20 breaths per
minute), elevated WBC count (above 12,000) and elevated or lowered body temperature (under 36 C (97 F) or
over 38 C (100 F)). Sepsis is differentiated from SIRS by the presence of a known pathogen. For example SIRS and
a positive blood culture for a pathogen indicates the presence of sepsis. Without a known infection, it's not
possible to classify the above symptoms as sepsis, only SIRS.
This immunological response causes widespread activation of acute-phase proteins, affecting the complement
system and the coagulation pathways, which then cause damage to the vasculature as well as to the organs.
Various neuroendocrine counter-regulatory systems are then activated as well, often compounding the problem.
Even with immediate and aggressive treatment, this may progress to multiple organ dysfunction syndrome and
eventually death.
Diagnosis
According to the American College of Chest Physicians and the Society of Critical Care Medicine,
[2]
there are
different levels of sepsis:
Systemic inflammatory response syndrome (SIRS). Defined by the presence of two or more of the following
findings:
o Body temperature < 36 C (97 F) or > 38 C (100 F) (hypothermia or fever).
o Heart rate > 90 beats per minute (tachycardia).
o Respiratory rate > 20 breaths per minute or, on blood gas, a P
a
CO
2
less than 32 mm Hg (4.3 kPa)
(tachypnea or hypocapnia due to hyperventilation).
o White blood cell count < 4,000 cells/mm
3
or > 12,000 cells/mm
3
(< 4 10
9
or > 12 10
9
cells/L),
or greater than 10% band forms (immature white blood cells). (leukopenia, leukocytosis, or bandemia).
Sepsis. Defined as SIRS in response to a confirmed infectious process. Infection can be suspected or proven (by
culture, stain, or polymerase chain reaction (PCR)), or a clinical syndrome pathognomonic for infection. Specific
evidence for infection includes WBCs in normally sterile fluid (such as urine or cerebrospinal fluid (CSF), evidence
of a perforated viscus (free air on abdominal x-ray or CT scan, signs of acute peritonitis), abnormal chest x-ray
(CXR) consistent with pneumonia (with focal opacification), or petechiae, purpura, or purpura fulminans
Severe sepsis. Defined as sepsis with organ dysfunction, hypoperfusion, or hypotension.
Septic shock. Defined as sepsis with refractory arterial hypotension or hypoperfusion abnormalities in spite of
adequate fluid resuscitation. Signs of systemic hypoperfusion may be either end-organ dysfunction or serum
lactate greater than 4 mmol/dL. Other signs include oliguria and altered mental status. Patients are defined as
having septic shock if they have sepsis plus hypotension after aggressive fluid resuscitation (typically upwards of 6
liters or 40 ml/kg of crystalloid).
Examples of end-organ dysfunction include the following:
[8]

Lungs
o acute lung injury (ALI) (PaO
2
/FiO
2
< 300) or acute respiratory distress syndrome (ARDS)
(PaO
2
/FiO
2
< 200)
Brain
o encephalopathy
symptoms:
agitation
confusion
coma
etiologies:
ischemia
hemorrhage
microthrombi
microabscesses
multifocal necrotizing leukoencephalopathy
Liver
o disruption of protein synthetic function: manifests acutely as progressive coagulopathy due to
inability to synthesize clotting factors
o disruption of metabolic functions: manifests as cessation of bilirubin metabolism, resulting in
elevated unconjugated serum bilirubin levels (indirect bilirubin)
Kidney
o oliguria and anuria
o electrolyte abnormalities
o volume overload
Heart
o systolic and diastolic heart failure, likely due to cytokines that depress myocyte function
o cellular damage, manifest as a troponin leak (although not necessarily ischemic in nature)
More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.
[9]

Cardiovascular dysfunction (after fluid resuscitation with at least 40 ml/kg of crystalloid)
o hypotension with blood pressure < 5th percentile for age or systolic blood pressure < 2 standard
deviations below normal for age, OR
o vasopressor requirement, OR
o two of the following criteria:
unexplained metabolic acidosis with base deficit > 5 mEq/L
lactic acidosis: serum lactate 2 times the upper limit of normal
oliguria (urine output < 0.5 ml/kg/hr)
prolonged capillary refill > 5 seconds
core to peripheral temperature difference > 3C
Respiratory dysfunction (in the absence of cyanotic heart disease or known chronic lung disease)
o the ratio of the arterial partial-pressure of oxygen to the fraction of oxygen in the gases inspired
(PaO
2
/FiO
2
) < 300 (the definition of acute lung injury), OR
o arterial partial-pressure of carbon dioxide (PaCO
2
) > 65 torr (20 mmHg) over baseline PaCO
2

(evidence of hypercapnic respiratory failure), OR
o supplemental oxygen requirement of greater than FiO
2
0.5 to maintain oxygen saturation 92%
Neurologic dysfunction
o Glasgow Coma Score (GCS) 11, OR
o altered mental status with drop in GCS of 3 or more points in a patient with developmental
delay/mental retardation
Hematologic dysfunction
o platelet count < 80,000/mm
3
or 50% drop from maximum in chronically thrombocytopenic
patients, OR
o international normalized ratio (INR) > 2
o Disseminated Intravascular Coagulation
Renal dysfunction
o serum creatinine 2 times the upper limit of normal for age or 2-fold increase in baseline
creatinine in patients with chronic kidney disease
Hepatic dysfunction (only applicable to infants > 1 month)
o total serum bilirubin 4 mg/dl, OR
o alanine aminotransferase (ALT) 2 times the upper limit of normal
Consensus definitions, however, continue to evolve, with the latest expanding the list of signs and symptoms of
sepsis to reflect clinical bedside experience.
[10]

Neonatal sepsis
Main article: Neonatal sepsis
In common clinical usage, sepsis specifically refers to the presence of a serious bacterial infection (SBI) (such as
meningitis, pneumonia, pyelonephritis, or gastroenteritis) in the setting of fever. Criteria with regards to
hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not
arise in neonates until death is imminent and unpreventable.
Treatment
Adults and children
The therapy of sepsis rests on antibiotics, surgical drainage of infected fluid collections, fluid replacement and
appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical
ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory
failure. Ensuring adequate nutritionpreferably by enteral feeding, but if necessary by parenteral nutritionis
important during prolonged illness.
A problem in the adequate management of septic patients has been the delay in administering therapy after sepsis
has been recognized. Published studies have demonstrated that for every hour delay in the administration of
appropriate antibiotic therapy there is an associated 7% rise in mortality. A large international collaboration was
established to educate people about sepsis and to improve patient outcomes with sepsis, entitled the "Surviving
Sepsis Campaign". The Campaign has published an evidence-based review of management strategies for severe
sepsis,
[5]
with the aim to publish a complete set of guidelines in subsequent years.
Early Goal Directed Therapy (EGDT), developed at Henry Ford Hospital by E. Rivers, MD, is a systematic approach
to resuscitation that has been validated in the treatment of severe sepsis and septic shock. It is meant to be
started in the Emergency Department. The theory is that one should use a step-wise approach, having the patient
meet physiologic goals, to optimize cardiac preload, afterload, and contractility, thus optimizing oxygen delivery to
the tissues.
[11]
A recent meta-analysis showed that EGDT provides a benefit on mortality in patients with sepsis.
[12]

As of December 2008 some controversy around its uses remains and a number of trials are ongoing in an attempt
to resolve this.
[13]

In EGDT, fluids are administered until the central venous pressure (CVP), as measured by a central venous
catheter, reaches 8-12 cm of water (or 10-15 cm of water in mechanically ventilated patients). Rapid
administration of several liters of isotonic crystalloid solution is usually required to achieve this. If the mean
arterial pressure is less than 65 mmHg or greater than 90 mmHg, vasopressors or vasodilators are given as needed
to reach the goal. Once these goals are met, the mixed venous oxygen saturation (SvO2), i.e., the oxygen
saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the SvO2 is less
than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the SvO2 is
optimized. Elective intubation may be performed to reduce oxygen demand if the SvO2 remains low despite
optimization of hemodynamics. Urine output is also monitored, with a minimum goal of 0.5 ml/kg/h. In the original
trial, mortality was cut from 46.5% in the control group to 30.5% in the intervention group.
[11]
The Surviving Sepsis
Campaign guidelines recommend EGDT for the initial resuscitation of the septic patient with a level B strength of
evidence (single randomized control trial).
[5]

Most therapies aimed at the inflammation process itself have failed to improve outcome, however drotrecogin
alfa (activated protein C, one of the coagulation factors) has been shown to decrease mortality from about 31% to
about 25% in severe sepsis. To qualify for drotrecogin alfa, a patient must have severe sepsis or septic shock with
an APACHE II score of 25 or greater and a low risk of bleeding.
[14]
However, since further trials have failed to
replicate this result, the use of activated protein C is controversial and is currently the subject of a large trial that
was demanded by the European Medicines Regulator.
[15]

During critical illness, a state of adrenal insufficiency and tissue resistance (the word 'relative' resistance should be
avoided
[16]
) to corticosteroids may occur. This has been termed critical illnessrelated corticosteroid
insufficiency.
[16]
Treatment with corticosteroids might be most beneficial in those with septic shock and early
severe acute respiratory distress syndrome (ARDS), whereas its role in other patients such as those with
pancreatitis or severe pneumonia is unclear.
[16]
These recommendations stem from studies showing benefits from
low dose hydrocortisone treatment for septic shock patients and methylprednisolone in ARDS
patients.
[17][18][19][20][21][22]
However, the exact way of determining corticosteroid insufficiency remains problematic.
It should be suspected in those poorly responding to resuscitation with fluids and vasopressors. ACTH stimulation
testing is not recommended to confirm the diagnosis.
[16]
Glucocorticoid drugs should be weaned and not stopped
abruptly.
In some cases, sepsis may lead to inadequate tissue perfusion and necrosis. As this may affect the extremities,
amputation may become necessary.
Neonates
Main article: Neonatal sepsis
Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until
hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are
frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative.
Prognosis

This section requires expansion.
Prognosis can be estimated with the MEDS score.
[23]
Approximately 2035% of patients with severe sepsis and 40
60% of patients with septic shock die within 30 days. Others die within the ensuing 6 months. Late deaths often
result from poorly controlled infection, immunosuppression, complications of intensive care, failure of multiple
organs, or the patient's underlying disease.
Prognostic stratification systems such as APACHE II indicate that factoring in the patient's age, underlying
condition, and various physiologic variables can yield estimates of the risk of dying of severe sepsis. Of the
individual covariates, the severity of underlying disease most strongly influences the risk of dying. Septic shock is
also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and
culture-negative severe sepsis.
Some patients may experience severe long term cognitive decline following an episode of severe sepsis, but the
absence of baseline neuropsychological data in most sepsis patients makes the incidence of this difficult to
quantify or to study.
[24]
A preliminary study of nine patients with septic shock showed abnormalities in seven
patients by MRI.
[25]

Epidemiology
In the United States, sepsis is the second-leading cause of death in non-coronary ICU patients, and the tenth-most-
common cause of death overall according to data from the Centers for Disease Control and Prevention (the first
being heart disease).
[26]
Sepsis is common and also more dangerous in elderly, immunocompromised, and critically
ill patients.
[27]
It occurs in 12% of all hospitalizations and accounts for as much as 25% of intensive-care unit (ICU)
bed utilization. It is a major cause of death in intensive-care units worldwide, with mortality rates that range from
20% for sepsis to 40% for severe sepsis to >60% for septic shock.
Research
Inflammatory signal blocker
A study reported in Science (journal) showed that SphK1 is highly elevated in inflammatory cells from patients with
sepsis and inhibition of the molecular pathway reduced the proinflammatory response triggered by bacterial
products in the human cells. Moreover, the study also showed the mortality rate of mice with experimental sepsis
was reduced when treated with a SphK1 blocker.
[28]

Nitric oxide
Medical research is focused on combating nitric oxide. Attempts to inhibit its production paradoxically led to a
worsening of the organ damage and in an increased lethality, both in animal models and in a clinical trial in sepsis
patients. In a study published in the Journal of Experimental Medicine, nitrite treatment, in sharp contrast with
the worsening effect of inhibiting NO-synthesis, significantly attenuates hypothermia, mitochondrial damage,
oxidative stress and dysfunction, tissue infarction, and mortality in mice
[29]

See also
Immune system
Intensive care
Meningococcemia
Multiple organ dysfunction syndrome
Pathogenic bacteria
Septic shock
Systemic inflammatory response syndrome





CAP (Community Acquired Pneumonia)

Community-acquired pneumonia (CAP) is one of the most common infectious diseases addressed by clinicians. CAP
is an important cause of mortality and morbidity worldwide.
Pathophysiology
CAP is usually acquired via inhalation or aspiration of pulmonary pathogenic organisms into a lung segment or
lobe. Less commonly, CAP results from secondary bacteremia from a distant source, such as Escherichia coli urinary
tract infection and/or bacteremia. CAP due to aspiration of oropharyngeal contents is the only form of CAP
involving multiple pathogens.
Frequency
United States
Patients who require hospital treatment for CAP are typically elderly persons and those with underlying chronic
obstructive pulmonary disease (COPD), such as chronic bronchitis (not emphysema). CAP is a common cause of
hospital admission, but statistics of patients treated for CAP in the ambulatory setting are difficult to obtain.
Overall, the incidence of CAP in 1994 was 170 cases per 10,000 individuals.
International
The prevalence of zoonotic CAPs is higher internationally than in the United States.
Mortality/Morbidity
Patients with severe CAP invariably have severe cardiopulmonary disease or diminished or absent splenic
function.
Mortality and morbidity rates of CAP are highest in elderly patients.
Race
CAP has no racial predilection.
Sex
CAP has no sexual predilection.
Age
CAP is particularly common in elderly adults, with an incidence rate in the United States of 280 cases per 10,000
individuals older than 65 years.
Clinical
History
Patients with community-acquired pneumonia (CAP) due to typical bacterial pathogens present with various
pulmonary symptoms, while those with CAP due to atypical pathogens present with a variety of both pulmonary
and extrapulmonary symptoms.
Patients with bacterial CAP typically present with variable degrees of fever, usually with a productive
cough and often with pleuritic chest pain.
The clinical presentation of CAP due to atypical pathogens is usually less acute than CAP due to typical
bacterial pathogens.
CAP due to atypical pathogens may have one or more extrapulmonary features, which is a clue to their
presence.
Patients with Legionella pneumonia may have a productive or nonproductive cough. In contrast, patients
with pneumonia due to Mycoplasma pneumoniae or Chlamydia pneumoniae usually present with a nonproductive
cough.
With the exception of Legionella pneumonia, chest pain is typically not a feature of CAP due to
nonzoonotic atypical pathogens.
Physical
Abnormal physical findings are confined to the chest in patients with typical bacterial CAP.
Rales are heard upon auscultation of the chest over the involved lobe or segment. If consolidation is
present, an increase in tactile fremitus, bronchial breathing, and E to A change may be present.
Pleural effusion (usually due to Haemophilus influenzae infection) that is large enough produces signs that
are detectable during physical examination. Patients with pleural effusion have decreased tactile fremitus and
dullness upon chest percussion. Pleural effusion in a patient with CAP and extrapulmonary manifestations should
suggest Legionella infection. Pleural effusion with appropriate epidemiologic history findings, such as contact with
a rabbit or deer, may suggest tularemia.
Purulent sputum is characteristic of pneumonia caused by typical bacterial pathogens but is typically not a
feature of that caused by atypical pathogens, with the exception of Legionnaires disease.
Blood-tinged sputum may be found in patients with pneumococcal infections, Klebsiella pneumonia, or
Legionella pneumonia.
Legionella pneumonia, Q fever, and psittacosis are atypical pneumonias that may present with signs of
consolidation. Consolidation is not a feature of pneumonia caused by M pneumoniae or C pneumoniae.
Patients with CAP who present with acute heart failure, such as acute myocardial infarction without pre-
existing congestive heart failure (CHF), often have normal cardiac silhouettes, bilateral symmetric moist rales, and
an S3 gallop rhythm upon auscultation.
Severe CAP is caused by the same spectrum of pathogens that cause mild or moderately severe CAP.
o The severity of CAP is determined by the pre-existing function of the heart, lungs, and spleen.
o The severity of CAP depends on host factors rather than on the type, number, or virulence of the
involved pathogens. However, with all other factors being equal, influenza, severe acute respiratory syndrome
(SARS), hantavirus pulmonary syndrome (HPS), and Legionnaires disease are not likely to present as severe CAP.
Causes
Typical bacterial pathogens
Typical bacterial pathogens that cause CAP include Streptococcus pneumoniae (both penicillin-sensitive and -
resistant strains), H influenzae (both ampicillin-sensitive and -resistant strains), and Moraxella catarrhalis (all
strains penicillin-resistant). These 3 pathogens account for approximately 85% of CAP cases. Images of Gram-
stained smears depicting Streptococcus pneumoniae, H influenzae, and Moraxella catarrhalis are seen below.

1 2 3
1.Gram stain showing Streptococcus pneumoniae.
2.Gram stain showing Haemophilus influenzae.
3.Gram stain showing Moraxella catarrhalis.
In patients with chronic bronchitis who develop CAP requiring hospitalization, M catarrhalis infection is
particularly common.
S pneumoniae remains the most common agent responsible for CAP.
Importantly, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa are not causes of CAP in
typical hosts.
S aureus causes CAP in the setting of postviral influenza.
K pneumoniae CAP occurs primarily in persons with chronic alcoholism.
P aeruginosa is a cause of CAP in patients with bronchiectasis or cystic fibrosis.
Other gram-negative pathogens rarely cause CAP.
Aspiration pneumonia is caused by the aspiration of oropharyngeal secretions into the lung. The extent of
aspiration and lobar distribution of the infiltrates depends on the patient's position at the time of aspiration.
Nearly all cases of CAP are due to a single pathogen. Exceptions occur but are rare.
Aspiration pneumonia is the only form of CAP caused by multiple pathogens.
Atypical pathogens
Atypical pneumonias can be divided into zoonotic and nonzoonotic atypical pathogens.
Zoonotic atypical pathogens that cause CAP include Chlamydia psittaci (psittacosis), Francisella tularensis
(tularemia), and Coxiella burnetii (Q fever).
Contact with the appropriate vector is required for these zoonotic pathogens to cause CAP.
A history of close contact with a parturient cat or sheep should be sought in patients with suspected Q
fever.
Psittacosis is preceded by recent close contact with psittacine birds.
Patients with tularemia have had recent close contact with deer or rabbits or have recently been bitten by
a tick or deer fly.
Nonzoonotic atypical pneumonias are caused by Legionella species, M pneumoniae, or C pneumoniae. These 3
pathogens account for approximately 15% of all CAP cases. Legionella species are the most important atypical
pathogens that cause CAP.
Typical and atypical pneumonias are differentiated based on the pattern of extrapulmonary findings rather than on
individual findings.
Typical bacterial pneumonias produce few, if any, extrapulmonary findings. In contrast, each atypical pathogen has
its own distribution pattern of extrapulmonary organ involvement, which permits an accurate and rapid
presumptive clinical diagnosis (as depicted in the image below).

Table 1. Differential Diagnostic Features of Atypical Pneumonias
1

Zoonotic Atypical Pneumonias Nonzoonotic Atypical Pneumonias
Key Characteristics Psittacosis Q Fever Tularemia Mycoplasma
Pneumonia
Legionnaires
Disease
Chlamydia
Pneumonia
Symptoms
Mental confusion +
Prominent
headache
+ +
Meningismus +
Myalgias + + + +
Ear pain
Pleuritic pain +
Abdominal pain +
Diarrhea +
Signs
Rash
(Horder
spots)

(erythema
multiforme)

Raynaud
phenomenon

Nonexudative
pharyngitis
+ + +
Hemoptysis + +
Lobar consolidation
Cardiac involvement
(endocarditis)

(myocarditis)

(myocarditis/
heart block/
pericarditis)

(endocarditis,
myocarditis)

Splenomegaly + +
Relative bradycardia + +
Chest Film
Infiltrate
Patchy/
consolidation
Patchy/
consolidation
Ovid
bodies
Patchy Patchy/
consolidation
Single
circumscribed
lesions
Bilateral hilar
adenopathy
+
Pleural effusion
+
(bloody)

(small)

(small/
moderate)

Zoonotic Atypical Pneumonias Nonzoonotic Atypical Pneumonias
Key Characteristics Psittacosis Q Fever Tularemia Mycoplasma
Pneumonia
Legionnaires
Disease
Chlamydia
Pneumonia
Symptoms
Mental confusion +
Prominent
headache
+ +
Meningismus +
Myalgias + + + +
Ear pain
Pleuritic pain +
Abdominal pain +
Diarrhea +
Signs
Rash
(Horder
spots)

(erythema
multiforme)

Raynaud
phenomenon

Nonexudative + + +
pharyngitis
Hemoptysis + +
Lobar consolidation
Cardiac involvement
(endocarditis)

(myocarditis)

(myocarditis/
heart block/
pericarditis)

(endocarditis,
myocarditis)

Splenomegaly + +
Relative bradycardia + +
Chest Film
Infiltrate
Patchy/
consolidation
Patchy/
consolidation
Ovid
bodies
Patchy Patchy/
consolidation
Single
circumscribed
lesions
Bilateral hilar
adenopathy
+
Pleural effusion
+
(bloody)

(small)

(small/
moderate)


Although Q fever and psittacosis are associated with relative bradycardia, these zoonotic pneumonias may be
excluded by a negative epidemiologic vector contact history finding.
If psittacosis and Q fever are eliminated from the diagnostic consideration by history, relative bradycardia in a
patient with CAP should suggest Legionnaires disease.
Because Legionella pneumonia has its own characteristic pattern of organ involvement, it is readily distinguished
from other typical and atypical pathogens (as depicted in the image below).
Some signs and symptoms are more important than others and can be expressed in a weighted diagnostic point
system, which is highly accurate in assisting the clinician with determining a clinical diagnosis of Legionnaires
disease (see Table 3).
Table 2. Relative Bradycardia
Determination and Evaluation of Relative Bradycardia
Inclusive criteria
The patient must be an adult (>12 y).
The patient must have a fever >101F.
The pulse must be taken while the patients temperature is elevated.
Exclusive criteria
The patient has normal sinus rhythm without arrhythmia, second- or third-
degree heart block, or pacemaker-induced rhythm.
Patient must not be receiving a beta-blocker, verapamil, or diltiazem.
Temperature-Pulse Relationships (temperature and corresponding pulse [beats/min])
Appropriate Pulse Relative Bradycardia
41.1C/106F = 150/min <140/min
40.6C/105F = 140/min <130/min
40.0C/104F = 130/min <120/min
39.5C/103F = 120/min <110/min
38.9C/102F = 110/min <100/min
Causes of Relative Bradycardia
Infectious causes
Legionella infection
Psittacosis
Q fever
Typhoid fever
Typhus
Malaria
Babesiosis
Leptospirosis
Yellow fever
Dengue fever
Rocky Mountain spotted fever
Tularemia
Salmonella infections
Noninfectious causes
Beta-blockers
CNS lesions
Lymphomas
Factitious fever
Drug fever
Determination and Evaluation of Relative Bradycardia
Inclusive criteria
The patient must be an adult (>12 y).
The patient must have a fever >101F.
The pulse must be taken while the patients
temperature is elevated.
Exclusive criteria
The patient has normal sinus rhythm
without arrhythmia, second- or third-degree
heart block, or pacemaker-induced rhythm.
Patient must not be receiving a beta-blocker,
verapamil, or diltiazem.
Temperature-Pulse Relationships (temperature and corresponding pulse [beats/min])
Appropriate Pulse Relative Bradycardia
41.1C/106F = 150/min <140/min
40.6C/105F = 140/min <130/min
40.0C/104F = 130/min <120/min
39.5C/103F = 120/min <110/min
38.9C/102F = 110/min <100/min
Causes of Relative Bradycardia
Infectious causes
Legionella infection
Psittacosis
Q fever
Typhoid fever
Typhus
Malaria
Babesiosis
Leptospirosis
Yellow fever
Dengue fever
Rocky Mountain spotted fever
Tularemia
Salmonella infections
Noninfectious causes
Beta-blockers
CNS lesions
Lymphomas
Factitious fever
Drug fever
Another clue to Legionnaires disease in a patient with CAP and relative bradycardia is the lack of response to beta-
lactam antibiotic treatment. If other causes of relative bradycardia are excluded, this is a clue because it is a
constant early finding in Legionnaires disease.
[#table3]Table 3. Modified Winthrop University Hospital Infectious Disease Division's Point System for Diagnosing
Legionnaires Disease in Adults
1

Clinical Features Qualifying Conditions Point Score
Temperature
>103F*
With relative bradycardia +5
Headache Acute onset +2
Mental
confusion/lethargy*
Not drug-induced +4
Ear pain Acute onset -3
Nonexudative
pharyngitis
Acute onset -3
Hoarseness Acute, not chronic -3
Sputum (purulent) Excluding chronic bronchitis -3
Hemoptysis* Mild/moderate -3
Chest pain (pleuritic) Rapidly progressive asymmetrical infiltrates* -3
(excluding severe influenza/SARS)
Loose stools/watery
diarrhea*
Not drug induced +3
Abdominal pain* With or without diarrhea +5
Renal failure* Acute, not chronic +5
Shock/hypotension* Not 2 to acute cardiac -5
/pulmonary causes +5
Splenomegaly Excluding non-CAP causes -5
Lack of response to
beta lactams
After 72 h (excluding viral pneumonias) +5
Laboratory Features
Chest radiography
Rapidly progressive asymmetrical infiltrates*
(excluding severe influenza/SARS)
+3
PO
2
with A-a gradient
(>35)*
(Excluding severe influenza/SARS) -5
Na + Acute onset +1
PO4 =* Acute onset +5
SGOT/SGPT (early
mild/transient)*
Acute onset +4
Total bilirubin Otherwise unexplained +1
LDH (>400)* Excluding HIV/PCP -5
CPK/aldolase Otherwise unexplained +4
CRP (>30) Acute onset +5
Cold agglutinins (1:64) Acute onset -5
Creatinine Acute onset +2
Microscopic hematuria* Excluding trauma, BPH, Foley catheter, bladder/renal neoplasms +2
Likelihood of Legionella Infection
Total Points >15, Legionella infection very likely

5-15, Legionella infection likely

<5 Legionella infection unlikely
Clinical Features Qualifying Conditions Point
Score
Temperature >103F* With relative bradycardia +5
Headache Acute onset +2
Mental confusion/lethargy* Not drug-induced +4
Ear pain Acute onset -3
Nonexudative pharyngitis Acute onset -3
Hoarseness Acute, not chronic -3
Sputum (purulent) Excluding chronic bronchitis -3
Hemoptysis* Mild/moderate -3
Chest pain (pleuritic)
Rapidly progressive asymmetrical infiltrates*
(excluding severe influenza/SARS)
-3
Loose stools/watery diarrhea* Not drug induced +3
Abdominal pain* With or without diarrhea +5
Renal failure* Acute, not chronic +5
Shock/hypotension* Not 2 to acute cardiac -5
/pulmonary causes +5
Splenomegaly Excluding non-CAP causes -5
Lack of response to beta lactams After 72 h (excluding viral pneumonias) +5
Laboratory Features
Chest radiography
Rapidly progressive asymmetrical infiltrates*
(excluding severe influenza/SARS)
+3
PO
2
with A-a gradient (>35)* (Excluding severe influenza/SARS) -5
Na + Acute onset +1
PO4 =* Acute onset +5
SGOT/SGPT (early mild/transient)* Acute onset +4
Total bilirubin Otherwise unexplained +1
LDH (>400)* Excluding HIV/PCP -5
CPK/aldolase Otherwise unexplained +4
CRP (>30) Acute onset +5
Cold agglutinins (1:64) Acute onset -5
Creatinine Acute onset +2
Microscopic hematuria* Excluding trauma, BPH, Foley catheter, bladder/renal neoplasms +2
Likelihood of Legionella Infection
Total Points >15, Legionella infection very likely

5-15, Legionella infection likely

<5 Legionella infection unlikely

*Otherwise unexplained (acute and associated with pneumonia)
In typical hosts, CAP does not present with shock. If CAP presents with shock, look for impaired or absent splenic
function. Disorders and therapies associated with impaired splenic function include the following:
2

Chronic alcoholism
Amyloidosis
Chronic active hepatitis
Fanconi syndrome
Hyposplenism in elderly patients
Immunoglobulin A (IgA) deficiency
Intestinal lymphangiectasia
Myeloproliferative disorders
Waldenstrm macroglobulinemia
Non-Hodgkin lymphoma
Celiac disease
Regional enteritis
Szary syndrome
Congenital asplenia
Splenectomy
Sickle cell trait/disease
Splenic infarcts
Splenic malignancies
Steroid therapy
Rheumatoid arthritis
Systemic lupus erythematosus (SLE)
Systemic mastocytosis
Systemic necrotizing vasculitis
Thyroiditis
Pulmonary embolism
Congestive heart failure or acute myocardial infarction
CAP that presents with shock in the absence of conditions associated with hyposplenism should prompt an
evaluation for mimics of pneumonia that manifest as pulmonary infiltrates on chest radiography, fever,
leukocytosis, and hypotension, such as acute myocardial infarction or acute pulmonary embolism.
If CAP manifests as shock without evidence of hyposplenia, acute myocardial infarction, or acute pulmonary
embolism, consider an exacerbation of pre-existing cardiopulmonary disease that presents with hypotension and
coronary insufficiency with hypoxemia or emphysema.
Nonpulmonary pathogens

Nonpulmonary pathogens that have been known to cause CAP include the following:
Nonaeruginosa pseudomonads
Stenotrophomonas (Xanthomonas) maltophilia
Citrobacter freundii
Burkholderia (Pseudomonas) cepacia
Citrobacter koseri
Enterobacter species
Flavobacterium species
Enterobacter cloacae
Flavobacterium meningisepticum
Enterobacter agglomerans
Enterococcus species

Treatment
Medical Care
Therapeutic principles in community-acquired pneumonia
Pathogens
o Single pathogens almost always cause community-acquired pneumonia (CAP). Multiple
pathogens rarely, if ever, cause CAP.
o CAP is almost never caused by more than one typical or two atypical organisms or multiple
typical/atypical organisms. Studies that report multiple pathogens are flawed and demonstrate one organism
microbiologically with serologic evidence of prior exposure to the other pathogen. Clinical experience has
demonstrated this principle for decades.
o The only cause of multiple-pathogen pneumonia is aspiration pneumonia.
Comorbid conditions
Comorbid conditions do not affect selection of antimicrobial therapy.
Monotherapy is as effective as multidrug therapy.
The addition and/or change of antibiotics based on severity of illness and/or comorbidities is irrational.
Antimicrobial therapy is directed against the pathogen rather than against the comorbid factors.
Comorbidity is an important prognostic factor and contributes to the severity index but has no place in antibiotic
selection.
Severity
o The severity of CAP is determined by underlying conditions of the lungs, heart, and spleen.
o Do not change antibiotics or use additional antibiotics to treat severe CAP.
o Additional antibiotics do not affect the pulmonary, cardiac, or splenic dysfunction that
determines clinical severity.
o CAP that presents with hypotension and/or shock is due to underlying lung disease, cardiac
disease, acute myocardial infarction, or an exacerbation of CHF.
o Antibiotic monotherapy is the same for mild, moderate, or severe CAP.
o Rapid cavitation is not a typical feature of CAP. CA-MRSA CAP presents as a fulminant CAP with
rapid cavitation and necrotizing pneumonia caused by CA-MRSA (SCC mec IV) with the PVL gene, which follows
influenza.
Appropriate empiric coverage
o In normal hosts, therapy does not need to cover S aureus, Klebsiella species, or P aeruginosa in
CAP. (Most CAP regimens include K pneumoniae coverage.) S aureus coverage should be included in patients with
influenza who have focal infiltrates.
o Most antibiotics used to treat community-acquired aspiration pneumonia (eg, doxycycline,
respiratory quinolones, beta-lactams) are highly effective against oral anaerobes. Metronidazole and clindamycin
are usually unnecessary. For aerobic lung abscesses, clindamycin or moxifloxacin is preferable.
o Coverage should include the typical (S pneumoniae, H influenzae, M catarrhalis) and atypical
(Legionella and Mycoplasma species, C pneumoniae) pathogens.
Therapeutic considerations
o Monotherapy coverage of both typical and atypical pathogens in CAP is preferred over double-
drug therapy.
o Monotherapy is less expensive and as effective as double-drug regimens.
o Avoid empiric macrolide monotherapy because approximately 25% of S pneumoniae strains are
naturally resistant to all macrolides.
o Preferred monotherapy for CAP includes doxycycline or a respiratory quinolone.
This is the least expensive way to optimally treat CAP.
No increased resistance is noted with extensive use.
No serious adverse effects are noted.
It is well tolerated in both oral and intravenous forms.
It is ideal for intravenous-to-oral switch monotherapy in terms of patient compliance, safety, and cost.
o In patients with CAP who are able to take oral medication, switch from intravenous to oral
administration after 48 hours, using an antibiotic with the appropriate spectrum, high bioavailability, minimal
adverse gastrointestinal effect profile, little or no resistance potential, and relatively low cost such as doxycycline
or a respiratory quinolone.
o Most penicillin resistance is relative resistance and is readily treatable with penicillin and/or
beta-lactams.
o Most highly penicillin-resistant S pneumoniae infections (minimum inhibitory concentration
[MIC] >2 g/mL) may also be treated with beta-lactams. Alternately, doxycycline or respiratory quinolones may be
used. Vancomycin is rarely, if ever, needed.
o Very highly penicillin-resistant S pneumoniae (MIC 6 g/mL) strains are a rare cause of CAP but
remain susceptible to ceftriaxone.
Treatment measures
Patients with CAP who are moderately to severely ill should be hospitalized. Factors that predict an
increased risk of mortality in patients with CAP have been studied and include older age, significant comorbidities,
increased respiratory rate, hypotension, fever, multilobar involvement, anemia, and hypoxia, among others.
Patients with severe CAP require admission to an intensive care unit (ICU). Oxygen and/or ventilatory
support may be required.
Because the severity of CAP frequently is due to underlying severe cardiopulmonary disease, direct
medical efforts at supporting cardiopulmonary function while administering antibiotics for CAP.
Patients admitted with severe CAP and hypotension or shock are often hypotensive because of an acute
pulmonary or cardiac insult such as pulmonary embolism or acute myocardial infarction.
If no acute cardiopulmonary explanation can be found (eg, exacerbation of severe underlying lung
disease, exacerbation of pre-existing CHF), patients with shock likely have diminished or absent splenic function.
o Many underlying conditions are associated with diminished splenic function that may manifest as
severe CAP (see Causes).
o An abdominal scar due to abdominal trauma or lymphoma staging is a probable sign that the
patient has asplenia.
o Howell-Jolly bodies in the peripheral blood smear in a patient presenting with CAP who is in
shock suggest hyposplenism. The first step in treating a patient in shock is effective intravascular volume
replacement. If aggressive intravascular replacement is inadequate, pressors may be added. Do not administer
pressors before adequate volume replacement because effective intracirculating intravascular volume will
decrease and the blood pressure will drop further.
Treatment of penicillin-resistant pneumococcal pneumonia is as follows:
o The overuse of beta-lactam and macrolide antibiotics has probably caused a gradual increase in
the S pneumoniae MIC. This relative increase in the MIC (ie, intermediate resistance or relative resistance) can be
overcome by using full recommended doses of beta-lactams.
o Most cases of penicillin-resistant S pneumoniae infection are still treated with penicillin. Most
strains have increased MICs but are still susceptible and are not clinically resistant to penicillin.
o Penicillin resistance is classified according to MICs. Breakpoints are as follows:
Sensitive - 0.6 g/mL or less
Intermediate resistance - 0.1-1 g/mL
Highly resistant - 2 g/mL or more
o Strains of pneumococci that are highly resistant to penicillin may be treated with levofloxacin,
the only quinolone indicated for the treatment of highly penicillin-resistant S pneumoniae. Alternatively,
vancomycin, clindamycin, or linezolid may be used.
o The use of non-C cell-wall active agents against S pneumoniae, such as doxycycline or
levofloxacin, does not increase penicillin resistance among pneumococci.
o The widespread use of macrolides and trimethoprim-sulfamethoxazole (TMP-SMX) and
tetracycline (excluding doxycycline) has been associated with penicillin-resistant S pneumoniae and multidrug-
resistant S pneumoniae.
o Most oral cephalosporins, except cefprozil, have been associated with increased S pneumoniae
resistance. Use of intravenous-to-oral switch programs is as follows:
Most patients with CAP who are admitted to the hospital are treated with empiric
intravenous antibiotic therapy. Unless these patients are acutely ill in the ICU or are unable to absorb medication
from the gastrointestinal tract, they may be switched to equivalent oral therapy to complete a 2-week course of
therapy after 48 hours.
Candidate agents for intravenous-to-oral switch programs have the same spectrum as
intravenous agents, excellent bioavailability, few adverse effects, low resistance potential, and relatively low cost.
Ideal agents for intravenous-to-oral switch programs include a respiratory quinolone or doxycycline.
o Other agents that may be used if S pneumoniae is not the etiologic agent include azithromycin or
clarithromycin.
Empiric therapy in hospitalized patients with community-acquired pneumonia

Suboptimal regimens include the following:
Monotherapy
o Ceftriaxone
Covers typical pathogens but not atypical pathogens
Adverse effects - Non Clostridium difficile diarrhea, pseudobiliary lithiasis
1 g IV q24h
o Azithromycin
Fails to cover approximately 25% of S pneumoniae strains
Should not be used alone
Covers atypical pathogens
Adverse effects - Nausea, vomiting, non C difficile diarrhea
Very low serum levels - Slow onset/delayed therapeutic effect
Moderately expensive
Combination therapy
o Ceftriaxone plus erythromycin
Covers typical and atypical organisms
Adverse effects - Nausea, vomiting, non C difficile diarrhea, phlebitis, cardiac effects
(QTc), pseudobiliary lithiasis
Most expensive combination
Intravenous-to-oral switch therapy - Disadvantage of double-drug therapy (relatively
expensive/inconvenient)
o Ceftriaxone plus azithromycin
Covers typical and atypical pathogens
Adverse effects - Nausea, vomiting, non C difficile diarrhea, phlebitis, cardiac effects
(QTc), pseudobiliary lithiasis
Intravenous-to-oral switch therapy - Disadvantage of double-drug therapy (relatively
expensive/inconvenient)
Optimal regimens include the following:
Monotherapy
o Typical CAP pathogens
Respiratory quinolone
Ceftriaxone
Ertapenem
o Typical CAP pathogens
Respiratory quinolone
Doxycycline
Empiric therapy for CAP in patients with HIV infection is as follows:
CAP in a patient with focal infiltrate on chest radiography and a CD4 count that exceeds 200 cells/L
o The most likely pathogens include S pneumoniae, H influenzae, M legionella, or C pneumoniae.
o Optimal empiric therapy in the context of extrapulmonary findings (atypical pathogens) is with
respiratory quinolone or doxycycline. In the absence of extrapulmonary findings (typical bacteria), ceftriaxone,
doxycycline, respiratory quinolone, or ertapenem should be used. In patients with CAP who have features of both
typical and atypical pathogens, respiratory quinolone or doxycycline should be used.
CAP in a patient with focal infiltrate on chest radiography and a very low CD4 count (<200 cells/L)
o The most likely pathogens include P jiroveci, M tuberculosis, Mycobacterium avium-intracellulare,
and Histoplasma capsulatum.
o Optimal empiric therapy for tuberculosis consists of isoniazid, ethambutol, rifampin, or
pyrazinamide. M avium-intracellulare infections are treated with azithromycin plus ethambutol and/or rifampin,
rifabutin, or azithromycin plus ethambutol plus respiratory quinolone. Histoplasmosis is treated with itraconazole
or amphotericin B.
Consultations
Patients with severe CAP should have the benefit of an infectious disease specialist to assist in the underlying
cause of severe CAP.
Diet
Diet in patients with CAP is as tolerated.
Activity
Patients with mild CAP may be treated in an ambulatory setting. Guide activity with common sense.
Medication
Before the role of atypical pathogens was appreciated, most patients with community-acquired pneumonia (CAP)
were treated with a parenteral beta-lactam antibiotic. Approximately 15% of patients with possible atypical
pneumonias were treated empirically with erythromycin or doxycycline.
Approximately 85% of CAP cases are caused by typical pathogens, such as S pneumoniae, H influenzae, or M
catarrhalis, and approximately 15% are due to the nonzoonotic atypical pathogens, such as Legionella species,
Mycoplasma species, or C pneumoniae. Atypical pathogens, such as Legionella species, were found to be important
causes of CAP. Because clinicians could not clinically differentiate typical pneumonias from atypical pneumonias,
combination therapy with a beta-lactam, such as ceftriaxone, in addition to erythromycin to cover both typical and
atypical pathogens, became popular.
Although clinically differentiating the typical from the atypical pneumonias with a reasonable degree of certainty is
possible, many clinicians empirically treat patients with CAP for both atypical and typical pathogens. Presently, a
preferred therapeutic approach to CAP is monotherapy with a respiratory quinolone such as levofloxacin.
The severity of CAP determines the route of antibiotic administration (ie, oral for mild cases, intravenous for
moderate-to-severe cases), predicts the necessity of admission to an ICU, predicts the duration of hospital stay,
and contributes to the prognosis.
Because patients with CAP have the same pathogen distribution regardless of clinical severity, the empiric
antibiotic treatment for CAP does not vary.
Because the severity of CAP is determined by cardiopulmonary or splenic function, using different antibiotics for
severe or less severe cases of CAP or adding additional antibiotics because the patient has severe CAP is illogical.
Antimicrobial therapy is directed against the microorganism and does not improve cardiopulmonary or splenic
function, regardless of the degree of severity.
Antibiotic, Penicillin & Beta-lactamase Inhibitor

Amoxicillin and clavulanate (Augmentin, Augmentin XR)
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate
inhibits beta-lactamaseproducing bacteria.
Good alternative antibiotic for patients allergic or intolerant to the macrolide class. Usually well tolerated and
provides good coverage to most infectious agents. Not effective against Mycoplasma and Legionella species. The
half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter cerebrospinal fluid.
For children > 3 months, base dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic
acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs
>40 kg.
Indicated for CAP caused by beta-lactamaseproducing bacteria with reduced susceptibility to penicillin (eg, H
influenzae, M catarrhalis, S pneumoniae). The extended-release product is available as amoxicillin 1000 mg and
clavulanate 62.5 mg.
Dosing
Interactions
Contraindications
Precautions
Adult
Extended-release: Amoxicillin 2 g/clavulanate 125 mg (ie, 2 extended-release tabs) PO q12h for 7-10 d
Pediatric
<3 months: 125 mg/5mL PO susp based on amoxicillin; 30 mg/kg/d divided bid for 7-10 d
>3 months: If using 200 mg/5 mL or 400 mg/5 mL susp, 45 mg/kg/d PO q12h; if using 125 mg/5 mL or 250 mg/5 mL
suspension, 40 mg/kg/d PO q8h for 7-10 d
>40 kg: Administer as in adults
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautionsAntibiotic, Tetracycline Derivative

Doxycycline (Vibramycin)
Much more active than tetracycline against many pathogens. Different adverse effect profile and pharmacokinetics
than tetracycline. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes,
causing arrest of RNA-dependent protein synthesis.
Dosing
Interactions
Contraindications
Precautions
Adult
100-200 mg PO/IV q12h
Pediatric
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV in 1-2 divided doses; not to exceed 200 mg/d
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautionsAntibiotic, Quinolone

Levofloxacin (Levaquin)
For pseudomonal infections and infections due to multidrug resistant gram-negative organisms.
Dosing
Interactions
Contraindications
Precautions
Adult
500 mg PO qd for 7-14 d
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautions
Moxifloxacin (Avelox)
Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.
Indicated for CAP, including multidrug-resistant S pneumoniae.
Dosing
Interactions
Contraindications
Precautions
Adult
400 mg PO/IV qd
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautionsAntibiotic, Carbapenem

Ertapenem (Invanz)
Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to
penicillin-binding proteins. Stable against hydrolysis by various beta-lactamases including penicillinases,
cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.
Dosing
Interactions
Contraindications
Precautions
Adult
1 g qd for 14 d if IV and 7 d if IM; infuse over 30 min if IV
CrCl <30 mL/min/1.73 m
2
: 500 mg IV qd
Pediatric
<3 months: Not established
3 months to 12 years: 15 mg/kg IV q12h; not to exceed 1 g/d
>12 years: Administer as in adults
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautionsAntibiotic, Macrolide

Azithromycin (Zithromax)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing arrest of RNA-
dependent protein synthesis.
Dosing
Interactions
Contraindications
Precautions
Adult
500 mg IV q24h for 3 d, then 500 mg/d PO for 7-10 d
Pediatric
<6 months: Not established
>6 months:
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
DosingInteractionsContraindicationsPrecautionsDosingInteractionsContraindicationsPrecautionsDosing
InteractionsContraindicationsPrecautionsAntibiotic, Cephalosporin (third Generation)

Ceftriaxone (Rocephin)
Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive
organisms, and higher efficacy against resistant organisms. Arrests bacterial cell-wall synthesis and inhibits
bacterial growth by binding to one or more of the penicillin-binding proteins.
Dosing
Interactions
Contraindications
Precautions
Adult
2 g IV q12-24h; not to exceed 4 g/d
Pediatric
Neonates > 7 d: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 100 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d

Dehidrasi adalah gangguan dalam keseimbangan cairan atau air pada tubuh. Hal ini terjadi karena pengeluaran air lebih banyak
daripada pemasukan (misalnya minum). Gangguan kehilangan cairan tubuh ini disertai dengan gangguan keseimbangan zat
elektrolit tubuh.
Dehidarasi terjadi karena
kekurangan zat natrium;
kekurangan air;
kekurangan natrium dan air.
Dehidrasi terbagi dalam tiga jenis berdasarkan penurunan berat badan, yaitu
Dehidrasi ringan (jika penurunan cairan tubuh 5 persen dari berat badan), dehidrasi sedang (jika penurunan cairan tubuh antara 5-
10 persen dari berat badan), dan dehidrasi berat (jika penurunan cairan tubuh lebih dari 10 persen dari berat badan).
Selain mengganggu keseimbangan tubuh, pada tingkat yang sudah sangat berat, dehidrasi bisa pula berujung pada penurunan
kesadaran, koma, hingga meninggal dunia, atau tidak.